Kalani L Raphael

University of Utah, Salt Lake City, Utah, United States

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Publications (13)63.11 Total impact

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    ABSTRACT: Low serum bicarbonate is a strong mortality risk factor in people with low estimated glomerular filtration rate (eGFR). It may also raise mortality risk in people with normal eGFR. This study investigated whether higher net endogenous acid production (NEAP), an estimate of net dietary acid intake and a risk factor for chronic kidney disease (CKD) progression, associates with higher mortality in people with and without low eGFR.
    Nephrology 11/2014; · 1.69 Impact Factor
  • Kalani L Raphael, Yingying Zhang, Jian Ying, Tom Greene
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    ABSTRACT: The prevalence of metabolic acidosis increases as glomerular filtration rate falls. However, most patients with stage 4 chronic kidney disease have normal serum bicarbonate concentration while some with stage 3 chronic kidney disease have low serum bicarbonate, suggesting that other factors contribute to generation of acidosis. The purpose of this study is to identify risk factors, other than reduced glomerular filtration rate, for reduced serum bicarbonate in chronic kidney disease.
    Nephrology 07/2014; · 1.69 Impact Factor
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    ABSTRACT: Background Low serum bicarbonate concentration is a risk factor for death in people with chronic kidney disease (CKD). Whether low serum bicarbonate is a mortality risk factor for people without CKD is unknown.Methods National Health and Nutrition Examination Survey III (NHANES III) adult participants were categorized into one of four serum bicarbonate categories: <22, 22-25, 26-30 and ≥31 mM. Cox models were used to determine the hazards of death in each serum bicarbonate category, using 26-30 mM as the reference group, in the (i) entire population, (ii) non-CKD subgroup and (iii) CKD subgroup.ResultsAfter adjusting for age, gender, race, estimated glomerular filtration rate, albuminuria, diuretic use, smoking, C-reactive protein, cardiovascular disease, protein intake, diabetes, hypertension, body mass index, lung disease and serum albumin, the hazards of death in the <22 mM serum bicarbonate category were 1.75 (95% CI: 1.12-2.74), 1.56 (95% CI: 0.78-3.09) and 2.56 (95% CI: 1.49-4.38) in the entire population, non-CKD subgroup and CKD subgroup, respectively, compared with the reference group. Hazard ratios in the other serum bicarbonate categories in the entire population and non-CKD and CKD subgroups did not differ from the reference group.Conclusions Among the NHANES III participants, low serum bicarbonate was not observed to be a strong predictor of mortality in people without CKD. However, low serum bicarbonate was associated with a 2.6-fold increased hazard of death in people with CKD.
    Nephrology Dialysis Transplantation 01/2013; · 3.37 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Higher serum total alkaline phosphatase (AP) levels are associated with increased serum C-reactive protein (CRP) levels and mortality in the general and CKD populations. It is unclear to what extent these associations are related to bone disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a nationally representative sample of 10,707 adult participants from the 1999-2004 National Health and Nutrition Examination Survey, serum nonskeletal AP levels were estimated from the measured serum skeletal and total AP levels. The associations of serum skeletal AP and nonskeletal AP levels with elevated serum CRP concentrations (>3 mg/L) and mortality were examined in multivariable models. RESULTS: Skeletal AP was not associated with elevated CRP (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR, 0.98; 95% CI, 0.75-1.28). In contrast, nonskeletal AP was associated with elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD: OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03). CONCLUSIONS: Bone disease is unlikely to account for the known associations of serum total AP with increased inflammation and mortality.
    Clinical Journal of the American Society of Nephrology 11/2012; · 5.07 Impact Factor
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    ABSTRACT: Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2)) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease.
    Kidney International 02/2012; 81(3):300-6. · 8.52 Impact Factor
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    ABSTRACT: Cognitive impairment is a risk factor for death in dialysis patients and the general population. We sought to determine if cognitive impairment is associated with death in people with non-dialysis-dependent chronic kidney disease (CKD), and if so, whether this relationship is greater in the CKD population compared to the general population. National Health and Nutrition Examination Survey-III participants older than 60 years were asked to subtract 3 from 20 five times and to perform immediate and delayed recall of three items. A cognitive score of 0-11 was assigned based on the number of correct responses. Participants were categorized according to cognitive score (11, 9-10, 6-9, and 0-5) and CKD status. Survival analyses were conducted using Cox models. Within the CKD subpopulation, those in the lowest cognitive score group had a twofold increased hazard of death compared to those with maximum score. Within the non-CKD subpopulation, those in the lowest cognitive score group had a 46% increased hazard of death compared to those with maximum score. However, the difference in the hazards of death in the CKD and non-CKD subpopulations with the lowest cognitive score was not significant (p = 0.99). Low cognitive score is associated with an increased risk of death in elderly individuals with and without CKD; however, there was no interaction of CKD and low cognitive score in this analysis.
    American Journal of Nephrology 12/2011; 35(1):49-57. · 2.62 Impact Factor
  • Kalani L Raphael, Alfred K Cheung
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    ABSTRACT: Despite many years of experience with hemodialysis, the outcomes of maintenance dialysis patients remain poor. The Frequent Hemodialysis Network-Daily (FHN-Daily) Trial found that six times per week in-center short hemodialysis decreased left ventricular mass and improved self-reported physical functioning over a 1-year intervention period compared with conventional thrice-weekly dialysis. Despite the promising results, caution is needed in the projection of these intermediate outcomes to hard clinical endpoints, such as cardiovascular events and death.
    Seminars in Dialysis 11/2011; 24(6):621-8. · 2.25 Impact Factor
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    ABSTRACT: Collecting duct (CD) adenylyl cyclase VI (AC6) has been implicated in arginine vasopressin (AVP)-stimulated renal water reabsorption. To evaluate the role of CD-derived AC6 in regulating water homeostasis, mice were generated with CD-specific knockout (KO) of AC6 using the Cre/loxP system. CD AC6 KO and controls were studied under normal water intake, chronically water loaded, or water deprived; all of these conditions were repeated in the presence of continuous administration of 1-desamino-8-d-arginine vasopressin (DDAVP). During normal water intake or after water deprivation, urine osmolality (U(osm)) was reduced in CD AC6 KO animals vs. controls. Similarly, U(osm) was decreased in CD AC6 KO mice vs. controls after water deprivation+DDAVP administration. Pair-fed (with controls) CD AC6 KO mice also had lower urine osmolality vs. controls. There were no detectable differences between KO and control animals in fluid intake or urine volume under any conditions. CD AC6 KO mice did not have altered plasma AVP levels vs. controls. AVP-stimulated cAMP accumulation was reduced in acutely isolated inner medullary CD (IMCD) from CD A6 KO vs. controls. Medullary aquaporin-2 (AQP2) protein expression was lower in CD AC6 KO mice vs. controls. There were no differences in urinary urea excretion or IMCD UT-A1 expression; however, IMCD UT-A3 expression was reduced in CD AC6 KO mice vs. controls. In summary, AC6 in the CD regulates renal water excretion, most likely through control of AVP-stimulated cAMP accumulation and AQP2.
    AJP Renal Physiology 09/2011; 302(1):F78-84. · 4.42 Impact Factor
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    ABSTRACT: Recent data suggest that elevated serum alkaline phosphatase levels are associated with increased mortality, but the mechanisms for this association are unknown. As metabolic syndrome is associated with higher serum alkaline phosphatase levels, we examined the joint association of mortality with metabolic syndrome and serum alkaline phosphatase levels in the US general population. Retrospective observational study of 15,234 adult participants in the National Health and Nutrition Examination Survey III. Multivariable Cox regression analyses were used to jointly relate mortality risk to serum alkaline phosphatase and indicators of metabolic syndrome. Prevalence of metabolic syndrome was 14% to 41% among patients in lowest and higher quartiles, respectively, for baseline serum alkaline phosphatase. The mortality hazard ratio for each doubling of serum alkaline phosphatase was 1.52 (95% confidence interval [CI], 1.35-1.72) adjusting only for demographic factors, and 1.37 (95% CI, 1.21-1.56) adjusting for both demographic and metabolic syndrome factors in the full cohort, and was 1.83 (95% CI, 1.36-2.46) adjusting for demographic factors in the subgroup without any of the component conditions of metabolic syndrome. In the US general population, higher levels of serum alkaline phosphatase is a predictor of mortality independent of the baseline prevalence of metabolic syndrome. Further studies are warranted to unravel the mechanisms of this association.
    The American journal of medicine 06/2011; 124(6):566.e1-7. · 5.30 Impact Factor
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    ABSTRACT: Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20-30 mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1 mmol/l, 46 ml/min per 1.73 m(2), and 326 mg/g of creatinine, respectively. Each 1 mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28-30 mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.
    Kidney International 10/2010; 79(3):356-62. · 8.52 Impact Factor
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    ABSTRACT: High serum alkaline phosphatase concentrations are associated with elevated serum C-reactive protein (CRP) levels in the general population. To examine whether this association is independent of serum vitamin D levels or modified in chronic kidney disease (CKD), we determined if such associations exist using data from the National Health and Nutrition Examination Survey III of 14,420 adult participants in which 5.7% had CKD (defined as estimated glomerular filtration rate < 60 ml/min per 1.73 m²). For each doubling of serum alkaline phosphatase, the odds of elevated serum CRP (over 3 mg/l) were increased 2.73-fold in the non-chronic and 2.50-fold in the CKD sub-populations, respectively. Regression coefficients of each doubling of serum alkaline phosphatase with elevated CRP were not significantly different in between the sub-populations. Additional adjustment for the serum 25-hydroxy (OH) vitamin D level did not substantively change the results. Thus, associations of serum alkaline phosphatase with elevated CRP are independent of serum 25-OH vitamin D in the chronic and non-CKD populations. Hence, serum alkaline phosphatase might be a marker of the inflammatory milieu.
    Kidney International 09/2010; 79(2):228-33. · 8.52 Impact Factor
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    ABSTRACT: Cystic epithelia in polycystic kidney disease display features similar to malignant cells. Thiazolidinediones have been shown to have anti-neoplastic properties, therefore we tested the hypothesis that pioglitazone reduces cyst formation, improves renal function, and prolongs survival in a mouse model of polycystic kidney disease. PC-Pkd1-KO mice, which have homozygous mutations of the Pkd1 gene in principal cells, were used. On the day after giving birth, mothers were fed standard mouse chow with or without pioglitazone (30 mg/kg chow). After weaning, the assigned diet was continued. At 1 month of age, blood pressure was measured and animals were sacrificed to determine kidney weight, body weight, and serum urea. Kidneys were evaluated for proliferation using Ki-67, apoptosis using TUNEL analysis, and cyst number using MRI. Survival was observed. Pioglitazone did not alter renal function, cell proliferation, apoptosis, or cyst formation in animals with polycystic kidney disease, however it did increase survival. Pioglitazone reduced blood pressure in PC-Pkd1-KO, but not in controls. These findings suggest that pioglitazone may have a unique antihypertensive effect in polycystic kidney disease, and that such an effect may promote improved survival.
    American Journal of Nephrology 09/2009; 30(5):468-73. · 2.62 Impact Factor
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    ABSTRACT: Renal cysts in autosomal dominant polycystic kidney disease arise from cells throughout the nephron, but there is an uncertainty as to whether both the intercalated cells (ICs) and principal cells (PCs) within the collecting duct give rise to cysts. To determine this, we crossed mice containing loxP sites within introns 1 and 4 of the Pkd1 gene with transgenic mice expressing Cre recombinase under control of the aquaporin-2 promoter or the B1 subunit of the proton ATPase promoter, thereby generating PC- or IC-specific knockout of Pkd1, respectively. Mice, that had Pkd1 deleted in the PCs, developed progressive cystic kidney disease evident during the first postnatal week and had an average lifespan of 8.2 weeks. There was no change in the cellular cAMP content or membrane aquaporin-2 expression in their kidneys. Cysts were present in the cortex and outer medulla but were absent in the papilla. Mice in which PKd1 was knocked out in the ICs had a very mild cystic phenotype as late as 13 weeks of age, limited to 1-2 cysts and confined to the outer rim of the kidney cortex. These mice lived to at least 1.5 years of age without evidence of early mortality. Our findings suggest that PCs are more important than ICs for cyst formation in polycystic kidney disease.
    Kidney International 02/2009; 75(6):626-33. · 8.52 Impact Factor