Science topic

Acute Kidney Injury - Science topic

Abrupt reduction in kidney function defined as an absolute increase in serum CREATININE of more than or equal to 0.3. mg/dl, a percentage increase in serum creatinine of more than or equal to 50%, or a reduction in urine output. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.
Questions related to Acute Kidney Injury
  • asked a question related to Acute Kidney Injury
Question
6 answers
In patients requiring renal biopsy due to AKI with high urea levels, is it advisable to perform dialysis through a catheter to improve platelet function? Transient normalization of urea levels through dialysis reduces the risk of bleeding after renal biopsy?
Relevant answer
Answer
Platelet uremic dysfunction is real for sure. I would start HD unless you have suspect AKI to have peaked and are expecting renal function to improve shortly. If I was worried about bleeding after biopsy I would also get DDAVP before the biopsy if I felt I needed the biopsy urgently (Ie vasculitis) because the results are going to immediately change my management.
  • asked a question related to Acute Kidney Injury
Question
7 answers
Patient's with chronic liver diseases who get admitted due to decompensation, have a grim path down the line. There is just worsening of scores as the time pass by & then the mortality hits them inspite of active interventions. Can we downgrade the scores in this population who get hospitalized within an ICU setting, (not undergoing any surgery) with any specific goal-directed targets that improve their survival rates?
Evidence :
The 3-month mortality for hospitalized patients not undergoing surgery was 4% for Child A, 14% for Child B, and 51% for Child C. A MELD score of 25 was associated with 30-day mortality of 50%.
Current evidence on goal-directed targets in Anaesthesia as part of Pre-operative care : Medical management undertaken to optimize cirrhotic patients undergoing surgery is usually directed toward treating active infection, optimizing central blood volume and renal status while minimizing ascites, and improving encephalopathy and coagulopathy. However, there is little evidence to support specific goal-directed targets for preoperative care.
  • asked a question related to Acute Kidney Injury
Question
3 answers
I am going to do MTT assay on HK-2 (adherent cell line) cells? I have checked many different protocols online but they are so diverse and now I am not sure which one will be suitable for my cell line. I would be grateful if I could get some pointers. Thanks.
1) My supervisor told me to not count the cells and directly plate 300 ul of my cell suspension to 48 well plate.
2) After I have plated my cells and left it overnight for cells to attach to the surface of the plate. I will be removing the media next day from the wells.
3) I have prepared different concentrations of sodium oxalate in my media which I will add to my cells at different time points.
4) When its time to add MTT solution, do I need to remove the media and add MTT solution, wait for 4 hours, and add solevent, and read the plate?
So my doubts are as follows?
1) Is it ok to remove the media in Step 2 (above) and add my stimulant which I have dissolved in the media for my desired concentration? My stock concentration of Sodium Oxalate is prepared in water.
2) In step 4, according to MTT assay protocol that the company provided, it says to add MTT solution directly to the wells without having to remove the media.
Any suggestions and advice will be great. Many thanks.
Relevant answer
Answer
Hi Ann,
If it can help you, you can take a look at the protocol we've followed to perform a cell proliferation assay in a recent study ( Exploring tumourigenic potential of the parasite Anisakis: a pilot study. Parasitol Res. 2018 Oct;117(10):3127-3136. doi: 10.1007/s00436-018-6008-2. Epub 2018 Jul 13. PMID: 30006808).
  • asked a question related to Acute Kidney Injury
Question
4 answers
I am always confronted with the dilemma of inserting a urinary catheter or not in patients with acute kidney injury for the sake of strict output monitoring. I would like to know what's the best evidence based practice for this issue. Thank you
Relevant answer
Answer
Condom catheters can be utilised in males that are not sedated/confused, without urinary obstruction or spinal cord injury.
  • asked a question related to Acute Kidney Injury
Question
3 answers
Acute Diarrhoeal Disease ( ADD ) is an important cause of Acute Kidney Injury (AKI) in developing countries. AKI is a preventable complication of ADD. The Haiti outbreak is due to a virulent strain of Cholera causing a very high mortality rate. As there is no data available on the incidence of AKI due to Cholera in Haiti, I request anyone who has published any data on the complications of cholera to provide the relevant information.
Relevant answer
Answer
Haiti reported 6,90,575 cases with 8346 deaths between 2010 - 2013 . Peru reported 6,83,487 cases with 4655 deaths between 1991 - 1996 . Zimbawe reported 1,28,208 cases with 5634 deaths between 2008 - 2009 . in 1994 , DR Congo reported 70,000 with 12, 000 deaths .
  • asked a question related to Acute Kidney Injury
Question
2 answers
Nause, vomiting and hiccups are common symptoms of uraemia. Dialysis is main treatment, however antiemetics can bring about symptomatic relief. This is more important in resource poor settings were dialysis may not be readily availbale and accessible due to cost.
Relevant answer
Hello Ikenna, maybe this document can be useful for you! (see the short summary of evidence-based therapy for symptoms in end-stage kidney disease -pag 419)
  • asked a question related to Acute Kidney Injury
Question
5 answers
I am trying to induce acute kidney injury in mice (male DBA/2j, 20-25 gr) by using gentamicin (80 mg/2ml). mice were treated with gentamicin (200 mg/Kg, i.p.) for 10 consecutive days.
I have diluted gentamicin (3 times) with normal saline in order to obtain a larger measurable volume for mice. 
Does this dilution affect the final concentration, as I didn't see any significant changes in BUN and serum creatinine 24 h after final injection?  
Relevant answer
Answer
Dear Sara,
Unfortunately, we had only an outbred stock of mice.
Later for in-depth research I used rats and the results were more stable (together with higher samples volume and easier collection of 24-hours urine samples)
  • asked a question related to Acute Kidney Injury
Question
4 answers
Hi everyone!
I am conducting a research in drug-induced nephrotoxicity. In your opinion, what would be the most suitable standard to define drug-induced nephrotoxicity case? Is it KDIGO Clinical Practice Guideline for AKI or NCI-CTCAE v4.0? Or maybe you have another preference.
Please see the attachment for more details.
Relevant answer
Answer
Thank you for the response, Daniel & Michaela
  • asked a question related to Acute Kidney Injury
Question
1 answer
Does anybody know the time interval between adminstration of lipopolysaccharide and the development of acute kidney injury in equines?
Relevant answer
  • asked a question related to Acute Kidney Injury
Question
1 answer
hi
I would like to measure fructose levels in urine samples, are there any suggestions for kits and methods? 
Relevant answer
Answer
We use the fructose/glucose/sucrose assay kits from Megazyme.
  • asked a question related to Acute Kidney Injury
  • asked a question related to Acute Kidney Injury
Question
9 answers
ACEI/ARBs dilate the efferent arterioles which is renal protective in long run. However, they should be held in acute kidney injury (AKI) to allow compensation and increased clearance. I am not sure if they should be held in a patient with rhabdo that has mildly impaired renal function.  A brief literature search and UpToDate search did not give a clear answer.
It would seem that keeping ACEI/ARB might be helpful (avoid increased pressure on glomerulous when toxin is present) but I could also see allowing arteriole construction might help maintain renal function. Anyone studied this, know of research or have evidence based thoughts? Could be a nice clinical study... 
Relevant answer
Answer
ACE inhibitor should be avoided in rhabdomyloysis as a cause of AKI, as ACE inhibitor may worse GFR, beside risk of severe huperkalemia.
  • asked a question related to Acute Kidney Injury
Question
1 answer
Hello
I am working on rat models of acute kidney injury that induce with glycerol and ischemia reperfusion.
I want to check therapeutic effects of mesenchymal stem cells of T cells subset in kidney by putting real-time PCR on target genes but this method has not been successful. I am looking for a better way for the my goal.
many thanks
razie
Relevant answer
Answer
FACS will help.
  • asked a question related to Acute Kidney Injury
Question
5 answers
I am working on murine model for ischemia reperfusion induced acute kidney injury. I am pretty confused about the type of treatment regimen I should follow- ie whether i should give pre treatment or post treatment to the animals (Wistar rats). Please suggest me the correct treatment plan.
Relevant answer
Answer
Hi Anuradha,
There are many questions you need to answer before you make this decision. What is your treatment: how do you think it works, how long before it starts to work, what is the half life of the treatment in vivo? Also consider clinical applications: ie. is this a treatment for trauma where in real life, you would not be able to pretreat, or transplantation or some other condition where you could? Finally, look through the literature and see what other people did, especially for your or similar treatments. This will help you decide on a treatment plan. Good luck!
  • asked a question related to Acute Kidney Injury
Question
1 answer
In my project, I tested sodium valproate on IR model of Balb/C mice. Although I applied routine procedure as mentioned in corresponsive papers for instance sodium valproate dissolved in normal saline and was injected intraperitoneal, also structural assay of this drug was tested. But unfortunately, the result was not reliable and reproducible.
In one experiment intensity of kidney injury in VPA (50 mg/kg) treated mice was similar to normal saline treated mice and in another experiment, the observed results were as following:
VPA (300 mg/kg) treated mice died and The severity of kidney injury in VPA (50 mg/kg) treated mice was more than VPA(150 mg/kg) treated mice and more than normal saline treated mice.
I am confused and I don’t know what is the reason for this observation. I will be grateful if anyone can help.
Relevant answer
Answer
Effects of sodium valproate on renal functions in rats.
Hergüner MO1, Altunbaşak S, Doğan A, Yildizdaş D, Incecik F, Erdoğan S, Gönlüşen G, Dağlioğlu K, Dikmen N, Burgut R.
Abstract
In recent years, it has been reported that sodium valproate occasionally can cause renal tubular impairment. This study was designed to demonstrate the renal tubular and glomerular functions in rats given sodium valproate as monotherapy, as well as to determine any reversibility of dysfunctions. Female rats were randomly allocated to three groups: group 1 received sodium valproate 500 mg/kg/d intraperitoneal for six weeks; after the same injection period, group 2 was housed for another six weeks, after which laboratory investigations were completed; and group 3 served as a control group made up of 20 healthy rats living in same condition without any treatment. Serum ALT, total protein, uric acid, ALP, phosphorus, sodium levels, and urine Ca/cr ratio were significantly different between groups 1 and 3 (p < 0.025), but this difference was not seen between groups 2 and 3. On the other hand, other parameters such as TRP, Ccr, NAG, and MDA were not significantly different among the three groups ( p > 0.025) These results suggest that SV does not have a significant dose- or time-related side effect on renal functions. Minor biochemical dysfunctions related to long-term sodium valproate therapy is reversible, and the minimal renal fibrosis that showed histopathologically is not clinically important. The renal tissues of rats are known to show similar metabolic and histological patterns with human renal tissues. No renal dysfunction was expected in humans because there were no clinically statistically significant renal side effects in this study.
  • asked a question related to Acute Kidney Injury
Question
22 answers
Hi
I need some help for time consuming methods. I have to calculate estimated Glomerular filtration rate (eGFR) for my study patients. These are 700 patients and I have calculate eGFR for each patient. Problematic thing for me is that I have to take 5 readings of eGFR during their followup (it means I have to take 3500 readings for all patients). Can anyone suggest me any online calculator which could provide me GFR all all patients once I enter required data. Or anyone share some spreadsheet made by himself or herself so I could use it to save my time.
I shall be very thankful to you.
Relevant answer
Answer
Please, attached is eGFR syntaxis of CKD-EPI equation...SCr_1 (serum Creatinine measurement 1). Please, change the name Scr-1 for your current creatinine name of each measurements. Then, run the syntaxis and the eGFR will be calculated on your database.
  • asked a question related to Acute Kidney Injury
Question
8 answers
Hi
I am evaluating renal recovery pattern among non-dialysis dependent AKI patients especially among patients with AKIN-I and AKIN-II stage of AKI. I am bit confuse because my outcome is renal recovery but available literature has vast variation for definition of renal recovery.
Most of the studies have been done on critically ill patients requiring dialysis. But in my case, patients have mild to moderate severity of AKI. There is no patient with dialysis in my study. So definition of dialysis independence will be excluded. On the other hand, as in my study patients are not critically ill and have less severe stage of AKI, so defining AKI as +/-25% of baseline will show that all patients have full recovery. However, most of the patients have elevated levels of Serum creatinine as compared to baseline. and I am confuse to declare them as fully renal recovery patients because I can not ignore the findings of previous studies that "small increase in serum creatinine is associated with high morbidity and mortality"
Please guide me in this regard, with appropriate reference
Relevant answer
Answer
Recovery process in patients followed-up due to acute kidney injury
K Magden,1 I Yildirim,1 ME Kutu,2 MC Ozdemir,2 S Peynir,2 A Altas,2 G Yildiz,3 and E Hur1
Abstract
Introduction: Acute kidney injury (AKI) may result in complete recovery in some of the patients and partial recovery in others. AKI episodes may accelerate the progression to chronic kidney disease and end-stage renal failure, while risk for morbidity and mortality is high following AKI. Discharge of patients from the hospital, independently from dialysis is a crucial outcome. Many patients without a need for dialysis, require follow-up for various durations and different treatments. The objective of this study was to compare mean recovery time of the patients followed-up due to prerenal, renal and postrenal AKIs.
Method: In this prospective observational study, a total of 159 patients hospitalized in Bulent Ecevit Hospital, clinic of nephrology or monitored in the other wards and intensive care unit due to AKI, between June 2011 and January 2012, were enrolled. The cases were divided into three groups as prerenal, renal and postrenal, and monitored with the daily visits and renal function testing.
Results: Prerenal AKI was seen by 54%, while renal AKI was observed by 34% and post-renal AKI by 12%. Incidence of chronic kidney disease was 17.6%. Totally 43 patients required hemodialysis (27%). Of these patients, 23 were in the prerenal AKI (53.4%), 15 in the renal AKI (34.8%) and 5 (11.6%) in the postrenal AKI group. Blood urea nitrogen (BUN) and creatinine levels were dropped to the basal values only in the prerenal AKI group, on the seventh day of treatment. These levels remained higher in the postrenal and renal groups on the 7th day of treatment compared to the basal values. BUN levels decreased to the normal values on average 7th day in the postrenal, while remained higher in the renal group.
Conclusion: Prerenal AKI patients recovered in seven days with a proper treatment, although AKI patients due to other reasons should be followed-up for a longer time.
  • asked a question related to Acute Kidney Injury
Question
4 answers
I encounter quite a good number of patients with Acute Kidney Injury (AKI) which developed subsequently following ingestion or parenteral intake of commonly used (ODC) NSAIDs. These are happening particularly in elderly patients with generalised bodyache/old or recent fractures & of course, with some old-age co-morbidity.
Relevant answer
Answer
The  best  way  to  prevent  AKI  induced  by  NSAIDs  is  to  avoid  the  usage. There  are  other  non - nephrotoxic  analgesics that  can  be  recommended  to  alleviate the pain.  But  despite  Kidney  disease  patients  if  compelled  to  receive NSAIDs the  best  options  are
1) To  choose  the  least  nephrotoxic  NSAID  at  the  lowest  dose ( Piroxicam  10 - 20 mg )
2)  Hydrate  the  patient  adequately
3 )  Avoid  combining   other  Nephrotoxic agents
4) Non - Pharmacological  methods to  alleviate  pain  should be  encouraged.
  • asked a question related to Acute Kidney Injury
Question
5 answers
I often find it challenging to clear patients with ESRD to proceed with renal transplant who also have asymptomatic moderate degree of aortic stenosis (which could progress to severe/critical AS within unpredictable period of time while awaiting for renal transplant).
1): Shall we clear those patients for renal transplant since they have acceptable surgical risks?
2): What are the possible clinical outcomes or best management strategy in case those patients became symptomatic from severe/critical AS within 1-2 years after renal transplant?
Any experience or suggestion?
Relevant answer
Answer
1. Yes. Ideally AVR prior to RT would make their surgical risks very low. But the anti coagulation would make logistic issues in a deceased donor transplant. The ebst would be to offer the transplant and then AVR.
2. From 2nd year post RT, they are "normal" individuals, other than for immunusuppressed status. They would benefit from AVR.
  • asked a question related to Acute Kidney Injury
Question
4 answers
I am working on surgically induced acute kidney injury. The model is showing an improvement in renal function after 48 hrs. Please tell me if it is common or is it due to some error in my experiment.
Relevant answer
Answer
Acute kidney failure happens when your kidneys suddenly lose the ability to eliminate excess salts, fluids, and waste materials from the blood. This elimination is the core of your kidneys’ main function. Body fluids can rise to dangerous levels when kidneys lose their filtering ability. The condition will also cause electrolytes and waste material to accumulate in your body, which can also be life-threatening.
Acute kidney failure is also called acute kidney injury or acute renal failure. It’s common in people who are already in the hospital. It may develop rapidly over a few hours. It can also develop over a few days to weeks. People who are critically ill and need intensive care have the highest risk of developing acute kidney failure.
Acute kidney failure can be life-threatening and requires intensive treatment. However, it may be reversible. If you’re in good health otherwise, recovery is possible.
  • asked a question related to Acute Kidney Injury
Question
4 answers
The routine practice in AKI patients is to adjust the dose of the medications as per eGFR (using MDRD or CKD-EPI equation), but my concern is that in someone with evolving AKI, using eGFR will significantly overestimate the actual GFR.
Is there a better method?
Relevant answer
Answer
I usually assumed that the GFR was zero or close to it in patients with AKI. All GFR calculations you quote are based on a steady state, and AKI is not a steady state, so I agree that they overestimate true GFR. Therefore, I assumed zero and dosed accordingly. Always follow drug levels when possible.
  • asked a question related to Acute Kidney Injury
Question
1 answer
I am researching acute kidney injury and the regulation of primary cilia length.
AKI induces shortening primary cilia, (we think that reacitve oxidative species (ROS) contributes those deciliation, but what molecules and enzyme are directly involve in those deciliation is unknown.
There are two candidates; katanin, spastin.
Do you have any idea??
Relevant answer
Answer
You should look at AuroraA, HDAC6... There is a review that just came out about ciliary disassembly (Liang, Meng, Zhu, Pan, Cell.Mol.Life Sci. february 2016, Mechanism of ciliary disassembly). I have no recollection of katanin or spastin being involved in cilia shortening...
  • asked a question related to Acute Kidney Injury
Question
6 answers
I working on study on AKI biomarkers. I had measured biomarkers in several timepoints: 6, 12, 18, 24 postproceduraly. I need to pick up the best timpoint for each biomarker. Is there option to combine ROC, p-values in logistic regression and timing to chose the best ? I found study by Krawczewski et al. They wrote: After weighting the AUC, timing measurement, and P values from predictive logistic models we selected 12-h cystatin C as the “optimal” time point”               Is there calculator to do this?
Thanks a lot
Relevant answer
Answer
Sorry Dra Marta Załęska-Kocięcka, I thought it would serve!!! I hope you find what you want. 
Cordially JM
  • asked a question related to Acute Kidney Injury
Question
8 answers
using citrate as anticoagolant in CRRT circuit needs calcium to prevent hypocalcemia .
What is the infusion protocol of calcium chloride and calcium gluconate ?
as i know cacl2 has more ionized ca than ca gluconate but in all protocol the concentration of cacl2 is higher than ca glu.
Relevant answer
Answer
There is a protocol from Berlin has been quite successful. 
Abstract
 
Objective: Citrate anticoagulation is an excellent alternative to heparin anticoagulation for critically ill patients requiring continuous renal replacement therapy. In this article, we provide a safe and an easy-to-handle citrate anticoagulation protocol with variable treatment doses and excellent control of the acid–base status.
Design: Prospective observational study.
Setting: University hospital.
Patients: One hundred sixty-two patients with acute renal failure requiring renal replacement therapy were enrolled in the study.
Intervention: A continuous venovenous hemodialysis-based citrate anticoagulation protocol using a 4% trisodium solution, a specially designed dialysate fluid, and a continuous calcium infusion were used. The study period was 6 days. Hemofilters were changed routinely after 72 hours of treatment. The patients were grouped according to body weight, with patients below 60 kg body weight in group 1, patients with at least 60 kg and up to 90 kg body weight in group 2, and patients with a body weight of above 90 kg in group 3. Dialysate flow was adapted according to body size and matched approximately 2 L/hr for a patient with average body size. Blood flow, citrate flow, and calcium flow were adjusted according to the dialysate flow used.
Measurements and Main Results: Median filter run time was 61.5 hours (interquartile range: 34.5–81.1 hours). Only 5% of all hemofilters had to be changed because of clotting. The prescribed treatment dose was achieved in all patients. Acid–base and electrolyte control were excellent in all groups. In the rare cases of metabolic disarrangement during citrate anticoagulation, acid–base values were rapidly corrected by modifying either the dialysate flow or alternatively the blood flow rate. Eight patients (5%) developed signs of citrate accumulation indicated by an increase of the total calcium >3 mmol/L or a need for high calcium substitution.
Conclusions: We provide a safe and an easy-to-handle citrate anticoagulation protocol that allows an excellent acid–base and electrolyte control in critically ill patients with acute renal failure. The protocol can be adapted to patients’ need, allowing a wide spectrum of treatment doses.
  • asked a question related to Acute Kidney Injury
Question
24 answers
In acute setting what is the validity of using eGFR calculation. It is only to CKD or it can be use in patients previously healthy who develops an AKI?
Relevant answer
Answer
Dear Dr Valarezo, thank you very much for your so kind appreciation of my intervention ed il mio apprezzamento per il cordiale saluto in italiano e per gli auguri che lericambio di cuore  
  • asked a question related to Acute Kidney Injury
Question
9 answers
I would like to ask you for help in interpretation of KDIGO criteria for AKI in periprocedural settings.
I have problem with criterium: increase in Scr by at least 26.1 mg/dl within 48 hours, when applying it to periprocedural AKI. Does the increase need to appear within 48h with baseline as reference? Or may the reference be a postprocedural measurement. Below you can find examples of both scenarios:
PATIENT1: baseline Cr: 100 mmol/l;
postprocedural Cr: 0h: 105 mmol/l; 12h: 110 mmol/l; 24h: 140mmol/l
PATIENT2: baseline Cr: 100 mmol/l;
postprocedural Cr: 0h: 80 mmol/l; 12h: 110 mmol/l; 24h: 120mmol/l
In both cases there is Scr increase over 26.1 mmol/l but in PATIENT 1 the reference is baseline and in PATIENT it is 0h.
Do they both have periprocedural AKI according to KDIGO criteria or is it only the first one?
Looking forward to your replies
Relevant answer
Answer
Thank you for your replies.
John W Pickering thank you for the interesting paper. 
It is very intuitive to refer to the baseline value. However, the 48h criterium (in KDIGO guidelines) is thought to be a moveable window. I feel that guidelines should precisely define periprocedural AKI. 
  • asked a question related to Acute Kidney Injury
Question
11 answers
I'm planning to evaluate the remedial effects of Mesenchymal Stem cells in glycerol induced acute kidney injury (AKI) so I want to find the right dose of glycerol to establish AKI in rats.
Relevant answer
Answer
Hi.. Can you guys give me the relevant references for following this model
  • asked a question related to Acute Kidney Injury
Question
8 answers
In my study, I designed a multivariate regression model for AKI among dengue patients. But recently, a reviewer of my paper objected that I have included many variables that are co-linear with AKI and to make my model more robust I should analyse non-colinear variables for the development of Model. Following is statement of reviewer
"In addition, with only 95 AKI patients, it is not appropriate to use more than 10 factors in the model for multivariate analysis. The authors have indeed included several collinear variables such as BUN with proteinuria, haematuria, glycosuria, urine leucocytes, dysuria and elevated Uric acid ; DHF and DSS; elevated ALT and transaminitis and rhabdomyolysis (which will have elevated AST); Oedema and Ascites ( but not hypoalbuminaemia?). Most of these individual variables are representatives of a similar disease process and the model needs to be improved with inclusion of clinically relevant non-collinear confounders to make it robust"
Can any one guide me about this issue, because I found many studies describing DHF and DSS as a risk factors of AKI, additionally rhabdomyolosis has been also reported to as a risk factors of AKI in previous studies. But here reviewer is objecting to include these variables. If I excludes these variables then I got only 2 or 3 risk factors that are not so much significant. How I can handle this issue?
Relevant answer
Answer
When performing multiple linear regression (MLR) there are any one of a number of preliminary steps that should be done before proceeding. Let's return to that in a moment and answer the question first.
When doing MLR with a decent computer program, the output will include a partial probability for each variable being indispensable to the regression process. There are established procedures for eliminating or adding variables.
One is bottoms up, one starts with a variable (your choice which), and sees if it contributes significantly to the effect (e.g. partial probability <0.1 or <0.05), if not, try another. If so, add another variable, and see if both add significantly to the outcome, if not, remove the one with the largest partial probability of not contributing. Then, add another variable. Repeat until a model is built of only significant factors.
Second method, top down. Put in all the variables and eliminate that variable with the highest likelihood of contributing nothing. Repeat until only significant variables remain.
Now, we skipped the preliminaries. Before you do any of this, examine how linear the relationships are between the individual variables. If they are not linear, make them linear. This is done by what is loosely called transformation of variables. Consider for example, if one examines the timing of events between two different occurrences that are correlated, that correlation and the linear behaviour of how those variables covary may be considerably improved by taking the reciprocals or logarithms of them (or square roots). Inspecting this for your ten variables and doing the appropriate transformations is likely to improve your final model markedly. Not to toot my own horn, but take a look at how variables are examined in "An improved method for determining renal sufficiency using volume of distribution and weight from bolus 99mTc-DTPA, two blood sample, paediatric data. Nuclear Medicine Communications 27(12): 961-968, 2006"
There are several other considerations of importance. The first is whether or not the variables are normally distributed, and the second is whether or not the difference between the model and the data has the same variability on the left hand side of the plot, as it does on the right. Often, when these differences called 'residuals' are plotted they look like the variability is the same at the minimum and maximum of the range. If so, this is called homoscedastic, and all is well. However, if those residuals look more like a fan than a flat 'bar' then the variables may be proportional, in which case transforming them to create homoscedasticity is appropriate (e.g., take the logs and plot that, and also they will correlate better). 
Normal or not normal. If a variable is not normally distributed, then that is a problem. For example, there are variables for which taking an average is meaningless, and a median would work better. Sometimes this is because the variable is A divided by B, where A and B are both normal, and their ratio may be a Cauchy distribution, which distribution is so unstable for looking at residuals that one would not insert it into MLR, it would ruin it. So one would use A and B separately in the MLR. Sometimes the ratio of A and B is normal when neither A nor B are normal. In that case, one would regress A/B in MLR and not A or B individually.
Good luck, it does take work. With practice, it takes not long at all to look at ten variables and come up with very good models. Without the tricks above, which are hardly the only way of doing things but probably the easiest to comprehend, one may fail to do justice to what the data is has in it. When in doubt, ask the data, it knows all. Does a t-test work better than a Wilcoxon test? Ask the data, it knows.
Finally, collinearity. Basically, it is a bad idea to regress height for weight with shoes on and as well as weight with shoes off. MRL diagnostics in a stats program will have a collinearity check in it. For example, see www.stat.ualberta.ca/statslabs/casestudies/files/childmu13.pdf
and search for collinearity. I find the reviewer's comment a bit off of the top, collinearity is something to worry about, but is at the bottom of a long list of other things to worry about first. And, collinearity interpretation is an art form, it is hard to understand at first.
  • asked a question related to Acute Kidney Injury
Question
12 answers
what is the use of furosemide in Acute Kidney Injury?
Relevant answer
Answer
AKI is a life threatening , but reversible renal disease . Early diagnosis of AKI in stage 1 & 2 can prevent progression to stage 3 AKI , requiring Dialysis . The treatment consists of adequate hydration , discontinue drugs such as NSAIDS , ACEI/ARB's & nephrotoxic antibiotics . At this stage the clinician has to decide , whether stage 1 & 2 would progress to stage 3 . The furosemide stress test is a valuable diagnostic tool to guide clinicians , as improvement in urine output would suggest that AKI can be reversed at stage 1 & 2 & he can pursue conservative treatment . It should be highlighted that stage 1 & 2 AKI can be treated by non nephrologist clinicians & they should be aware of the diagnostic & therapeutic guidelines . This would be very relevant in developing countries .
  • asked a question related to Acute Kidney Injury
Question
6 answers
3 year male child with cold aiha with acute kidney injury with abnormal LFT with altered sensorium secondary to PRES. Has a large LV thrombus.infectious and preliminary malignancy workup negative. ANA PROFILE strongly positive for anti RO antibody. Aiha responded to ivig. But persistent poor sensorium and renal shutdown on PD. NO fever.
Relevant answer
Answer
hi, good morning, like gabriele casirati, the main concern looks the haemophagocitic syndrome, which not always presents with all the classical picture ( and evolves over time - fever is more common than splenomegaly), and either primary or secondary may be rather serious and rapidly evolving to a fatal condition - the hlh04 protocol is easily acessible on net and the sweden group has been very helpful, in clinical and lab advice - thr mail contacts are in the last pages of the protocol
Bon courage
How I treat hemophagocytic lymphohistiocytosis - Blood ...
  • asked a question related to Acute Kidney Injury
Question
4 answers
Bradykinin related peptides are constituents of venoms of different origins. One of the major effect of envenomation is multiple organ injuries, most commonly kidney injury. Bradykinin is responsible for vasodilation and thus hypotension. I would like to know if bradykinin related peptides (and thus vasodilation/hypotension) can lead to kidney injury.
Relevant answer
Answer
Considering the low target pressures during cardiopulmonary bypass surgery in the  attached paper it seems that hypotension per se does not suffice to induce AKI at least in this clinical setting. In my experience, it often (but certainly not always) takes the combination of two or more factors (e.g., hypoxia, anemia, pre-existing kidney disease, endothelial dysfunction, nephrotoxic drugs etc.) to induce AKI.  
  • asked a question related to Acute Kidney Injury
Question
5 answers
I utilize Gambro Prismaflex system - Prismocitrate 18/0 (CVVHDF).
Could you be so kind as to send me such a protocol?
Relevant answer
Answer
Hello Tomasz. I have attached our CRRT guidelines from the Vanderbilt Children's Hospital. We have used this with great success. Our regional citrate anticoagulation protocol is found on the last page of the attached document. I hope this helps.
  • asked a question related to Acute Kidney Injury
Question
13 answers
364      
KIM-1, NGAL, NAG, alpha-1 microglobulin, cystatin-c or vitamin-D binding protein.
Of above all, which 'one' biomarker should I consider to indicate an overall kidney damage in the patients exposed to higher levels of herbicides.
Relevant answer
Answer
Hi Carl, the kinetic (e)GFR reference is: Chen, S. (2013). Retooling the Creatinine Clearance Equation to Estimate Kinetic GFR when the Plasma Creatinine Is Changing Acutely. Journal of the American Society of Nephrology : JASN, 24(6), 877–888. doi:10.1681/ASN.2012070653
It's yet to be validated in many populations.
We've shown a 4hour creatinine clearance has value in the ICU but not a specifically nephrotoxic population. Pickering, J. W., Frampton, C. M., Walker, R. J., Shaw, G. M., & Endre, Z. H. (2012). Four hour creatinine clearance is better than plasma creatinine for monitoring renal function in critically ill patients. Critical Care (London, England), 16(3), R107. doi:10.1186/cc11391
I agree that attempting to measure GFR is more ideal, especially if only one measure is needed - I understand most GFR measurements take ~4hours. If, though, it is a matter of monitoring GFR then technicium based measures may not be able to be repeated.  There is, however, some work by Rabito and colleagues of a continuous monitoring of GFR.  Also Bruce Molitoris's group is working on dual fluorescence for monitoring GFR (still only animal experimentation at this stage I think).  A couple of references:
Rabito, C. A., Halpern, E. F., Scott, J., & Tolkoff-Rubin, N. (2010). Accurate, fast, and convenient measurement of glomerular filtration rate in potential renal transplant donors. Transplantation, 90(5), 510–517. doi:10.1097/TP.0b013e3181e9139d
Yu, W., Sandoval, R. M., & Molitoris, B. A. (2007). Rapid determination of renal filtration function using an optical ratiometric imaging approach. American Journal of Physiology-Renal Physiology, 292(6), F1873–80. doi:10.1152/ajprenal.00218.2006
  • asked a question related to Acute Kidney Injury
Question
3 answers
I am researching the issue of acute kidney injury as a systemic disease, with mechanisms of production and augmentation of a global diseminated inflammatory state, in a vicious circle with catastrophic consecuences, a sort of biological tsunami.
Relevant answer
Answer
This article is helpful for your question! 
Curr Opin Crit Care. 2014 Dec;20(6):613-9. doi: 10.1097/MCC.0000000000000150.
Systemic consequences of acute kidney injury.
Druml W1.
Author information
Abstract
PURPOSE OF REVIEW:
Acute kidney injury (AKI) is a frequent and serious event associated with a high rate of complications, with an increased risk of progression to multiple organ dysfunction and excessive 'attributable' mortality. AKI affects all physiologic functions and organ systems with interrelated mechanisms, including the 'classical' consequences of the uremic state, the inflammatory nature of AKI per se and resulting systemic effects, the modulating effect of AKI in the presence of an (inflammatory) underlying disease process and the multiple untoward effects induced by renal replacement therapy (RRT) and anticoagulation.
RECENT FINDINGS:
A rapidly increasing body of evidence is clarifying these systemic effects that are the reflection of a broad common pathology that ultimately results in an 'augmented' inflammation and impairment of immunocompetence. This includes the release of cytokines and inflammatory mediators, increase in oxidative stress, activation of various immune cells, neutrophil extravasation, generalized endothelial injury, increased vascular permeability and tissue oedema formation.
SUMMARY:
These systemic phenomena associated with AKI induce distant organ injury affecting all organ systems with clinically the most relevant effects being exerted on the lungs, the intestines and liver and the heart and predispose the progression to multiple organ dysfunction syndrome and death. Currently available renal replacement therapy modalities are incapable of compensating for these systemic consequences of AKI.
  • asked a question related to Acute Kidney Injury
Question
41 answers
The distinction between HRS and ATN can be clinically uncertain (if biopsy is under risk).
Relevant answer
Answer
Dear Adrian and Dear Zmicer
Adrian, I agree with your last comment.  Then, one can conclude that HRS is a prerenal, non responding to vascular volume expanders and non renal parenchimal condition,  exclusive of cirrhotic patients ,occurring spontaneously or secondary to a precipitating factor. Right?
It leads to answer  Zmicer´s question :Type 1 hepatorenal syndrome (HRS) does not  lead to acute tubular necrosis (ATN) in the absence of other insult.
Best regards both
  • asked a question related to Acute Kidney Injury
Question
4 answers
Is there any link between CIAKI and hypoxia and vitamin D3 metabolism? 
Relevant answer
Answer
Thanks All ! Currently, I am going through all the literature, got some connection with respect to cancer models, or some other context, But, trying to connect and correlate this in Acute Kidney Injury is difficult ! 
  • asked a question related to Acute Kidney Injury
Question
1 answer
I'm seeking published articles which declare marine resources as an anti-urolithiatic agents.
Relevant answer
Answer
The Protection of Polysaccharide from the Brown Seaweed Sargassum graminifolium against Ethylene Glycol-Induced Mitochondrial Damage.
Chao-Yan Zhang, Ting-Kong, Wen-Hui Wu and Min-Bo Lan.
Marine Drugs2013, 11, 870-880.
  • asked a question related to Acute Kidney Injury
Question
4 answers
Would FENa less than one apply for a situation like prerenal AKI with underlying CKD?
Relevant answer
Answer
It is preferable to use the KDIGO criteria for diagnosis of AKI  which is defined by a) rise in serum creatinine of 0.3 mg / dl in 48 hrs above baseline  b) rise in serum creatinine of 1.5 times above baseline in 1 week & c) Urine output < 0.5 ml / kg / hr for 6 - 12 hrs . The severity is further classified as Stage 1,2 & 3 .
 It is preferable to avoid the term prerenal AKI , primarily because renal biomarkers are raised even in prerenal , suggesting that renal injury has occurred . The concept that prerenal AKI is only due to hemodynamic factors with no renal injury is questioned , because of raised renal biomarkers . Prerenal AKI might fit into Stage 1 & 2 .
 The FeNa in CKD might be different in salt losing CKD due to chronic Interstitial nephritis , compared to chronic glomerulonephritis . Therefore , this parameter may be variable due to other factors .
  • asked a question related to Acute Kidney Injury
Question
6 answers
If to study the effects of kidney disease on patient using only blood samples what all aspects can be screened in blood apart from looking for specific biomarkers (ie., NAG, NGAL, KIM1 etc) and RBC/WBC cell count.
What about genetics/genomics? can it be implicated on blood samples to come to any kind of conclusions about any specific thing?
Using limited resources (ie., blood as the only means of assessment) can we generate enough valuable information to reach a specific conclusion? Ie., in this particular case for example what kind of genetic and biological changes could occur in a kidney disease patient (if cause is due to heavy metal toxicity and not due to hypertension or diabetes) that can be significantly assessed (apart from kidney biomarkers) using blood sample of the patient.
Relevant answer
Answer
it is impossbile to use the blood as an only screening tool for early kidney disease . I suggest urine sample is very imporatnt . Besides, urine biomarker (KIM-1)is very important . You can try serum component of amyloid A in advanced of CKD disease.
  • asked a question related to Acute Kidney Injury
Question
18 answers
Continuous renal replacement therapies can either combine convection and diffusion (CVVHDF) or preponderate one over the other (CVVH or CVVHD). Besides, there are other non continuous (24h) options such as SLED that can also be used.
Relevant answer
Answer
We use predominantly CVVHD in this setting. And following the same evidence as Stephen Lapinsky we prefer citrate, unless systemic heparinisation is indicated for another reason. Historically we avoided citrate in patients with liver dysfunction, but are using it more and more in these patients too, especially if the liver function has "stabilised", i.e. not worsening each day.
  • asked a question related to Acute Kidney Injury
Question
1 answer
Acute renal failure in severe Malaria has been defined as serum creatinine of 3mg% or more . In the recent RIFLE Criteria , Acute Kidney Injury (AKI ) has been defined as Risk : sr . creatinine : 1.5 - 1.9 : Injury : 2.0 -3.0 ; Failure : 3.0 mg% or more ( if normal creatinine is taken as 1.0 mg% ) . We feel that AKI in severe Malaria should be defined as sr. creatinine > 1.5 mg% . For eg . if a patient with fever due to malaria has a blood urea of 100 mg% & sr creatinine of 2.8mg% , this will not be classified as severe malaria in the existing guidelines , but in the RIFLE criteria , it should be classified as AKI . This has implications in treatment , as this patient has to be treated as severe Malaria . We have found this modification very useful in detecting severe Malaria early & starting treatment early .
Relevant answer
Answer
Clinicians should be aware of the recent KDIGO guidelines for the diagnosis of AKI . This has merged the RIFLE criteria evolved by ADQI & the AKIN criteria & classified them as stage 1 , 2 & 3 , which is similar to the RIFLE criteria & included a rise of serum creatinine by 0.3 mg/dl above baseline in 48 hrs . As community acquired AKI is gaining importance as a cause of morbidity & mortality in developing countries , it is essential that uniform criteria is utilized for diagnosing local community acquired AKI which can be due to multiple factors . This should also apply to malarial AKI . The KDIGO guidelines should be made available to primary & secondary care clinicians in both rural & urban areas of developing countries & not only to tertiary care nephrologists .
  • asked a question related to Acute Kidney Injury
Question
7 answers
Most observational studies on community-acquired acute kidney injury use hospital admission and relevant ICD codes as their study outcome. However, we have access to a primary care data base that can be linked to laboratory data and this may allow us to additionally study renal outcomes that did not require hospital admission and those that were not primarily attributed to AKI.
Relevant answer
Answer
Dr Tobias Dreischulte has stated that this study was done to evaluate AKI in a cohort group of hypertensive patients to quantify the risk of a certain drug exposure in the community . I shall briefly share my experience on AKI in elderly hypertensive patients . Elderly patients admitted for fractures are assessed by me for fitness for surgery .If a female patient has a serum creatinine of 1.3 mgs% or more & a male patient with serum creatinine of 1.5 mgs% , the surgery is postponed by 48-72 hrs . Most of these patients are hypertensives on ACEI / ARB , who are also taking NSAIDS for osteoarthritis & also pain of fractures . I have to immediately assess whether the rise in creatinine is due AKI or CKD . Since these patients are hypertensives , they would have some record of baseline creatinine done as a routine about 1-2 years ago . The ACEI / ARB are withdrawn & replaced with Calcium Channel Blockers . The NSAIDS are also withdrawn & replaced with Paracetamol . They are adequately hydrated with IV fluids ( 0.9% Saline ) . The serum creatinine is checked daily & a drop of serum creatinine is misleading as John Pickering highlighted , but reassuring ! If there are no complications of AKI , they would undergo surgery & at discharge , the creatinine done would be considered as baseline . The patients are very anxious & it is my duty to explain to them whether it is AKI or CKD . The delay in surgery improves renal function & prevents AKI from progressing stage 1 & 2 to stage 3 .
  • asked a question related to Acute Kidney Injury
Question
5 answers
I want to determine how many granulocytes infiltrate the kidneys in response to a toxin. How do I quantify them with absolute cell counts?
My method briefly: Digest kidney with collagenase & DNase, lyse RBCs, and spin over a 40/70% percoll gradient, isolate cells at interphase and stain with cd45, cd11b, and Ly6G/GR-1. I gate on CD45+ cells.
The light scatter (Fsc&Ssc) leaves a lot to be desired so I cannot determine cell number as percentage of viable/non-debris events. Any ideas on how to quantify other than cytospin?
Relevant answer
Answer
Hello Evan,
I would use counting beads either from Spherotech (accucount) or Invitrogen (Accucheck beads, count bright) or Bangs lab (Absolute counts). These are just volumetric standards that will estimate the volume of sample analysed, from which you will deduce your cell concentration. There are the BD True Counts tubes, but they are designed to be used in a Lyse no wash method. They are certainly more accurate.
Depending on the level of accuracy you want to achieve, I would forego the Percoll phase as you may lose some cells, It would be better to include a live dead label to exclude dead cells, CD45 to identify your Granulocytes by SSC/CD45 dot plot and I would NOT wash as you can gate on live cells. The less you manipulate your samples, the more accurate your counts will be.
Also, to normalize between samples I would weigh the samples before digestion and use a cell number/per unit of mass.
  • asked a question related to Acute Kidney Injury
Question
12 answers
Is it best to use a plasma only technique (insulin?) or plasma and urine?
Relevant answer
Answer
The best method probably depends on the context: if the purpose of measurement is a study the inulin method by the constant infusion technique with plasma measurements (see for example Montanari A et al., Am J Physiol 2012; 303:648) could be a good option. In the daily clinical practice, short periods of creatinine clearance calculation (even 2 hour- periods of clearance, in patients with bladder catheter, see Herrera-Gutierrez ME et al., Int Care Med 2007; 33:1900) can be used. Creatinine to estimate GFR in ICU patients by formulas (mainly developed for CKD) can be used only if renal function is stable, (i.e. serum creatinine is not changing along a 48 hour period).