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ABSTRACT: There are conflicting data regarding the comparative efficacy of mycophenolate mofetil (MMF) versus azathioprine (AZA) as maintenance immunosuppressive agent in kidney transplantation. The data are even less in combination with tacrolimus (TAC) in living donor kidney transplantation. A total of 205 living donor kidney transplants, on TAC-based triple drug immunosuppression were included in the study. A total of 113 patients received AZA and rest 92 were on MMF based protocol. TAC levels were monitored and graft biopsy was done whenever rejection was suspected. The outcomes were evaluated in terms acute rejection (AR) episodes at 1 year, infections, renal function, graft loss, and death between two groups. The study group comprised 163 males (79.5%) and 42 (20.5%) females. The mean age of patients was 42.4±11.8 years in the AZA group and 39.4 ±13.4 in the MMF group (P=0.09). The mean duration of follow-up was 491.7±240.7 and 478.8±334.4 days respectively in the AZA and MMF groups (P=0.75). Thirty-seven of 92 (40.2%) patients in the MMF group and 70/113 (61.9%) patients in the AZA group received IL-2 RAb induction (P=0.002). 32 patients (15.6 %) developed AR within a year. The incidence of AR was similar in patients who received MMF (12/92, 13%) and those who received AZA (20/113, 17.5%), (P=0.36). There was no difference in the incidence of AR in the subgroup of patients who received IL-2 RAb compared to those who did not receive induction in the two groups (5/37 vs. 7/55 in the MMF group and 10/70 vs. 10/43 in the AZA group, P=0.72). The incidence of infections was similar in the two groups (19/92, 20.6% vs. 25/113, 22.1%, P=0.79). Three patients developed CMV disease, of which two were in the MMF group. Graft loss occurred in 7/205 (3.4%) and death in 8/205 (3.9%) patients. Six of eight patients who died had functioning grafts. The rate of graft loss (3/92 vs. 4/113, P=0.97) and death (5/92 vs. 3/113, P=0.27) was similar in two groups. The overall patient survival was 94.5% and death censored graft survival was 97.4%. Cost comparison suggests AZA to be 6-10 times cheaper than MMF. This study suggests that, in tacrolimus-based immunosuppression, azathioprine may be as good as MMF as maintenance immunosuppressive drug in living donor kidney transplantation. It is also a more cost-effective immunosuppression.
Indian Journal of Nephrology 10/2011; 21(4):258-63.
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ABSTRACT: The aim of the study was to study the distribution of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its association with steroid responsiveness in children with idiopathic nephrotic syndrome (INS). One hundred twenty-five children with INS were classified into two groups: steroid-sensitive nephrotic syndrome (SSNS: n = 90) and steroid-resistant nephrotic syndrome (SRNS: n=35). The control group consisted of 150 unrelated healthy children. Genomic DNA was extracted from peripheral leucocytes by the standard salting-out method. ACE genotyping was performed and ACE genotypes DD, ID, and II were compared between different groups. The frequency distribution of the DD genotype was significantly increased in children with INS compared to control subjects (P = 0.0012) while the difference was not significant (P = 0.071) between SSNS and control subjects. The frequency distribution of the DD genotype was significantly high in the SRNS group compared to control subjects (P < 0.0001). The distribution of the DD genotype was high in SRNS compared to SSNS group patients (P = 0.016). In conclusion, the presence of the DD genotype may predict risk for steroid resistance in childhood INS.
Indian Journal of Nephrology 01/2011; 21(1):26-9.
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ABSTRACT: We prospectively studied 19 children with severe hypertension to evaluate the spectrum of radiological changes, severity and reversibility of this entity. All of them were subjected to clinical and biochemical evaluation, followed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Headache was seen in 17 children, 13 had confusion and drowsiness, 12 had nausea and vomiting, 10 patients had visual disturbances, seizure and dyspnoea. Only two had focal neurological deficit (one with right facial palsy and another with right lateral rectus palsy). Of these 19 children, 15 patients had hypertensive retinopathy and four had normal fundi. The positive MRI findings in 17/19 patients were: bilateral leukoencephalopathic changes in occipitoparietal region (9/17), diffuse white/grey matter lesion (3/17) patients, brain stem hyperintensity (2/17) and haemorrhagic lesions (3/17). On MRA, 12/19 patients had attenuation of cerebral arteries of different degree. On follow up, MRI findings resolved in all except three patients. All patients had normal MRA on follow up, except one with persistent minimal attenuation of middle cerebral artery and another had spasm in anterior, middle and posterior cerebral arteries. The intracranial abnormalities in these patients with severe hypertension were reversible in many of the cases after control of blood pressure was achieved. We therefore conclude that severe hypertension may lead to leuoencephalopathy, which had a wide radiological spectrum. A better understanding of this complex syndrome may obviate unnecessary investigations and allow management of associated problems in prompt and appropriate ways.
The British journal of radiology 06/2007; 80(954):422-9. · 2.11 Impact Factor
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ABSTRACT: A retrospective analysis of 67 biopsy proven cases of focal segmental glomerulosclerosis (FSGS) in children was performed. After a mean duration of disease of 48.5 ± 44 months, 20 patients (30%) achieved sustained remission (SR), 23 (34%) had frequent relapses (FR) and 24 (36%) were steroid non-responders (NR). the NR group had a significantly higher mean age of onset 9.1 ± 1.01 years (P= 0.003) and had higher number of females (P= 0.0009). They also had a significantly higher prevalence of microhaematuria as compared to FR and SR groups (P= 0.002). the initial steroid response category (P<0.00001) and the percentage of glomeruli with segmental sclerosis on histopathology (P= 0.001) correlated with the subsequent outcome. During this period six children developed progressive renal failure and all of them belonged to NR group (25%). There were four deaths and all of them were non-responders (16.6%). Features predictive of a poor therapeutic outcome in childhood FSGS are age of onset more than 9 years, female sex, microhaematuria, renal dysfunction at onset, initial non-response to steroids and percentage of glomeruli with segmental sclerosis on histopathology.
Nephrology 04/2007; 3(6):407 - 410. · 1.31 Impact Factor
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ABSTRACT: Background: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C.Methods: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400–800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 μg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period.Results: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 ± 147.6 and 104.8 ± 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 ± 114.9 IU/L at baseline to 71 ± 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy.Conclusion: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment.
Clinical Transplantation 10/2006; 20(6):677 - 683. · 1.67 Impact Factor
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ABSTRACT: Nephrotic syndrome is one of the commonest renal problem encountered in children. It is difficult to predict at onset, the clinical course in terms of steroid responsiveness or resistance. Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical course in common multi-factorial diseases including focal segmental glomerulosclerosis. There is no study available from our country till date to find out any correlation of the steroid response in idiopathic nephrotic syndrome and ACE gene polymorphism.
To study distribution and correlation of ACE gene I/D polymorphism in idiopathic steroid sensitive nephrotic syndrome.
Case-control retrospective study.
We studied ACE gene polymorphism in 90 consecutive patients (82% males, 18% females) with steroid sensitive idiopathic nephrotic syndrome and 300 normal controls (NC).
Chi-square test and Fisher's exact test (for cases with insufficient expected cell frequencies).
The mean age of onset was 5.3 +/- 4 years. Steroid sensitive (SS) patients showed II (SS-48%, NC-26%) genotype was more frequent than normal controls (p=0.002). There was no significant difference in genotype frequencies among steroid SS subgroups.
In our study II genotype was more frequent in steroid sensitive nephrotic syndrome children in comparison to normal controls. Further functional studies with large number of children are required to investigate the role of II genotype in steroid sensitive nephrotic syndrome. Comparison of the genotypic frequency with steroid resistant patients may provide information, which might be useful in clinical practice.
Indian Journal of Medical Sciences 10/2005; 59(10):431-5.
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ABSTRACT: Infections are a major cause of morbidity and mortality in chronic hemodialysis patients. This single center prospective study was carried out to determine the incidence and risk factors for infection in hemodialysis patients and plan appropriate strategies to reduce the risk of infection. A total of 84 consecutive patients who were initiated on hemodialysis over a 2-year period were followed until they either received a kidney transplant or died. In our hospital, as a policy, patients are offered hemodialysis as a bridge therapy to a kidney transplant. The mean duration of follow up was 3 months (range 1-11.8 months). The factors associated with at least one episode of infection were evaluated. Statistical analysis was done by multivariate stepwise logistic regression method. Fifty-one patients had a total of 57 episodes (67.8%) of infection. Of the 44 episodes of acute bacterial infections, vascular access exit site infection was the commonest followed by septicemia (13 patients, 29.5%). Staphylococcus aureus was the commonest bacterial isolate observed in 14 patients. On multivariate analysis, three risk factors for infection were identified: (1) nonarteriovenous fistula (AVF) vascular access for hemodialysis (p = 0.02), (2) increased number of hemodialysis sessions (p = 0.03), and (3) lower serum calcium level (p = 0.02). NonAVF vascular access was found to be the most important risk factor for infection in hemodialysis patients. Creation of an AV fistula, preferably at an early stage, appears beneficial for minimizing the risk of infection even in patients who are on short-term hemodialysis as a bridge therapy towards a kidney transplant.
Renal Failure 12/2003; 25(6):967-73. · 0.82 Impact Factor
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ABSTRACT: Neonatal anuria is not an uncommon problem in neonates. Here, we report an unusual case of neonatal anuria due to renal tubular dysgenesis, secondary to the use of angiotensin converting enzyme inhibitor (ACEI) during pregnancy. ACEI remains one of the most commonly used antihypertensive drug at present. A greater awareness needs to be created in the medical fraternity especially among pediatricians, gynecologists and internists that ACE inhibitors should not be prescribed during any trimester of pregnancy.
Indian pediatrics 04/2003; 40(3):258-60. · 1.05 Impact Factor
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Transplantation Proceedings 03/2003; 35(1):225-6. · 1.00 Impact Factor
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Transplantation Proceedings 03/2003; 35(1):266-7. · 1.00 Impact Factor
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ABSTRACT: There are few data regarding adolescent-onset nephrotic syndrome (NS) and no guidelines for biopsy criteria and treatment protocol. This study was conducted to analyze the clinical spectrum of adolescent-onset NS and evaluate possible biopsy criteria in these children. A prospective analysis was carried out on all patients with idiopathic NS (fulfilling the ISKDC criteria) with onset between 1 and 18 years of age. They were evaluated clinically, followed by biochemical investigations and kidney biopsy. These characteristics of patients with onset between 1 and 12 years (group A) were compared with the same parameters in patients with onset between 12 and 18 years of age (group B) referred to our hospital over the same period. Among all clinical parameters, microhematuria was significantly more prevalent in adolescents (P<0.001). Kidney biopsy was performed in 88% of adolescent patients. Focal segmental glomerulosclerosis (FSGS) was the most-common histopathology in group B (46.3%) compared with minimal change disease (MCD) in group A (42.9%). Group B had a significantly higher frequency of membranoproliferative glomerulonephritis (MPGN) (P<0.005) and a significantly lower frequency of MCD (P<0.001). The biochemical parameters at the onset were similar. On comparing microhematuria, hypertension, and renal insufficiency at presentation, we observed that two or more of these features were present in all patients with MPGN and only in 19.6% of adolescents with MCD, mesangioproliferative glomerulonephritis, and FSGS. The frequency of steroid resistance was significantly higher in group B (P<0.001). In conclusion, adolescent-onset NS differs from the childhood variety in having a significantly higher frequency of hematuria, steroid resistance, and evidence of non-MCD, especially MPGN, on histopathology. Kidney biopsy can be restricted to those adolescents who have at least two abnormal clinical/biochemical features or are steroid non-responders.
Pediatric Nephrology 12/2001; 16(12):1045-8. · 2.52 Impact Factor
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Indian pediatrics 11/2001; 38(10):1171-3. · 1.05 Impact Factor
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ABSTRACT: The treatment of frequently relapsing (FR) and steroid-dependent (SD) idiopathic nephrotic syndrome (INS) with oral cyclophosphamide (OCP) poses problems of compliance, side-effects and infections.
We prospectively evaluated the usefulness of intravenous cyclophosphamide (IVCP) in children with steroid sensitive INS who were frequent relapsers or steroid dependent. Fifty-one children were included in the study of whom 22 were FR and 29 were SD. IVCP was administered in a dose of 500 mg/m(2)/month for 6 months after achieving a steroid-induced remission. The response to IVCP was evaluated in terms of remission, change in the steroid response status of the patient, duration of remission (i.e. proteinuria-free days), side effects and compliance with therapy.
The proteinuria-free days (mean 19.9+/-3.5 before IVCP therapy vs 1256+/-167 days after IVCP therapy) (P<0.00001), and serum albumin levels (23+/-1.6 g/l before IVCP therapy vs 34+/-2 g/l after IVCP therapy) (P<0.001) were significantly higher following IVCP therapy. The cumulative remission rate in the study group was 49% at 5 years and was comparable to that achieved with oral cyclophosphamide at a 40% lower cumulative dose.
We conclude that IVCP is a safe and effective therapeutic modality in children with INS who are FR and SD. Its efficacy is comparable to the results obtained with oral cyclophosphamide based on historical comparisons with previous studies.
Nephrology Dialysis Transplantation 10/2001; 16(10):2013-7. · 3.40 Impact Factor
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ABSTRACT: 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).
Clinical Transplantation 07/2001; 15(3):173-5. · 1.67 Impact Factor
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Indian pediatrics 05/2001; 38(4):407-10. · 1.05 Impact Factor
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ABSTRACT: Glomerular diseases in children, although similar in histological appearance to those in adults, may have a better prognosis. There is much controversy regarding the prognostic factors in idiopathic focal segmental glomerulosclerosis (FSGS), especially the comparative prognosis of children and adults. A comparative analysis was carried out of 36 consecutive biopsy-proven cases of idiopathic FSGS presenting early in life ['early onset' as seen in children < or =12 years (group I)] and 36 cases presenting later ['late-onset' as seen in older children >12 years and adults (group II)]. Patients were compared for clinical, biochemical, and histopathological features, as well as disease outcome. A significantly higher prevalence of hypertension (P=0.002) and microscopic hematuria was seen in group II (P=0.02). There were no differences between the two groups in glomerular filtration rates corrected for body surface area at initial presentation (92+/-11 ml/min/1.73 m2 vs. 94+/-14 ml/min/1.73 m2). Patients with 'late-onset' FSGS had a significantly higher number of glomeruli with segmental sclerosis (P=0.007), more mesangial matrix expansion (P=0.009), greater mesangial cellularity (P=0.003), and significantly higher blood vessel involvement (P=0.03) than those with 'early onset' FSGS. There was a significantly higher response to steroids in group I (82.3%) than group II (36.4%) (P<0.02). At the end of the study period, 2 patients in group I and 11 in group II had developed persistent renal failure (P=0.01). Thus 'early onset' FSGS is more common in males, has significantly lower prevalence of hypertension and microscopic hematuria, with less-severe histopathological involvement, is more often steroid responsive, and has a better prognosis than 'late-onset' FSGS.
Pediatric Nephrology 10/2000; 14(10-11):960-4. · 2.52 Impact Factor
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ABSTRACT: A prospective study was conducted to evaluate the role of intravenous pulse cyclophosphamide (IVCP) infusions in the management of children with steroid resistant (SR) idiopathic focal segmental glomerulosclerosis (FSGS).
The study group comprised of 20 consecutive children with idiopathic nephrotic syndrome secondary to FSGS who were SR. All of them were subjected to standard baseline investigations. They were started on monthly infusions of IVCP in a dose of 500-750 mg/m2. Adjunctive prednisolone was given in a dose of 60 mg/m2/day for 4 weeks followed by 40 mg/m2/alternate day for another 4 weeks and tapered off over next 4 weeks.
The study group comprised of 15 boys and 5 girls with mean age of onset of disease of 5.5 +/- 3.5 years. Two of these children had chronic renal insufficiency prior to starting therapy. At the end of the study, after a mean duration of disease (since onset of NS) of 77 +/- 55 months, all 20 children had normal renal functions. After a mean follow up post IVCP therapy of 21.2 +/- 13.4 months, 13 of the 20 children (65%) had attained a complete remission. Of these, 10 children were infrequent relapsers, 2 frequent relapsers and 1 steroid dependent. The mean duration of remission following last dose of IVCP in these children was 12.5 +/- 11.9 months. Of the 7 children who continued to be proteinuric, 3 became edema free and have not required any albumin infusion or diuretics. One other died due to peritonitis 2 years after the last dose of IVCP. The mean total protein and serum albumin levels following the IVCP infusion were significantly higher than those prior to therapy (6.5+/-1.0 mg/dl Vs 5.0+/-0.8) (p=0.0004) and (3.5+/-0.7 g/dl Vs 2.3+/0.7) (p = 0.000007) respectively. The serum creatinine levels following IVCP therapy (0.8+/-0.2 mg/dl) were significantly lower than those prior to treatment (1.0+/-0.6 mg/dl) (p=0.02). The only side effects that were observed were transient nausea and vomiting during infusion (n=2) and alopecia (n=1). None of the children developed leukopenia or hemorrhagic cystitis.
IVCP infusions appear to be safe, effective and economical therapeutic modality in steroid resistant children with idiopathic FSGS.
Indian pediatrics 03/2000; 37(2):141-8. · 1.05 Impact Factor
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ABSTRACT: Acute renal failure (ARF) associated with liver disease is a commonly encountered clinical problem of varied etiology and high mortality. We have prospectively analyzed patients with liver disease and ARF to determine the etiology, clinical spectrum, prognosis and factors affecting the outcome. Other than hepatorenal syndrome patients, out of 221 cases, 66 developed ARF secondary to various liver disease like cirrhosis (n = 29, mortality 8, risk factors-older age p < 0.01, grade III/IV encephalopathy p < 0.05), fulminant hepatic failure (n = 25, mortality 15, risk factor-prolonged prothrombin time p < 0.01), and obstructive jaundice (n = 12, mortality 7, risk factor-sepsis p < 0.01). In these three groups the factors leading to ARF were volume depletion (24), gastrointestinal bleed (28), sepsis (34), drugs (27) [aminoglycosides (9) and NSAID (18)] along with hyperbilirubinemia. Various types of ARF with contemporaneous liver injury were malaria (n = 37, mortality 15, risk factors-higher bilirubin p < 0.001, higher creatinine p < 0.05, anuria p < 0.05 and dialysis dependency p < 0.05), sepsis (n = 36, mortality 22, risk factors-age p < 0.001, higher bilirubin p < 0.01, oliguria p < 0.05), hypovolemia with ischemic hepatic injury (n = 14, mortality 5, risk factors-higher creatinine p < 0.05 and SGPT p < 0.01), acute pancreatitis (n = 12, mortality 4, risk factors-higher bilirubin p < 0.001, higher SGPT p < 0.01, dialysis dependency p < 0.05), rifampicin toxicity (n = 10, no mortality), paroxysmal nocturnal hemoglobinuria (n = 3, no mortality), CuSO4 poisoning (n = 3 mortality 2), post abortal (n = 11, mortality 6, risk factors higher creatinine p < 0.05 and SGPT p < 0.01), ARF following delivery including HELLP syndrome (n = 12, mortality 4, risk factors-higher bilirubin p < 0.01 and SGPT p < 0.01), and of uncertain etiology (n= 14 mortality 4). 133 patients (60.2%), required hemodialysis hemodialfiltration or peritoneal dialysis. ARF associated with liver disease is having high mortality (42.5%). Avoidance of dehydration, hypotension, nephrotoxic drugs and sepsis, with promote dialytic support are necessary to reduce mortality and morbidity.
Renal Failure 01/2000; 22(5):623-34. · 0.82 Impact Factor
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ABSTRACT: This study was conducted to analyze the trend of histopathologic subtypes in idiopathic nephrotic syndrome (INS) in a homogenous racial group in India population. A prospective analysis of 400 consecutive children with INS was performed. Kidney biopsies were performed according to standard indications. Steroids were administered following the Arbeitsgeminschaft fur Padiatrische Nephrologie protocol. Cyclophosphamide was administered to children in the frequent-relapser, steroid-dependent, and steroid-nonresponder categories. Of the various histopathologic subtypes, focal segmental glomerulosclerosis (FSGS) was the most common (87 of 222 subtypes; 39.1%). Children who underwent biopsy between July 1992 and December 1996 (group B, n = 157) were compared with our initial published data of biopsies performed between January 1990 and June 1992 (group A, n = 65), with similar indications for biopsy in both groups. The incidence of FSGS was significantly greater in biopsies performed in the recent period (group B, 47% versus group A, 20%; P = 0.0002). The different clinical and biochemical parameters were also analyzed to differentiate FSGS from the other 2 subtypes. Hypertension (P = 0. 005), renal insufficiency at presentation (P = 0.001), and steroid resistance (P = 0.0006) were significantly greater in children with FSGS. On follow-up (mean, 5.4 years), children with FSGS were at a significantly greater risk for developing renal insufficiency (P = 0. 0001). We conclude there is a shift toward an increasing prevalence of FSGS over the years in the Indian population. This trend has immense therapeutic and prognostic significance.
American Journal of Kidney Diseases 11/1999; 34(4):646-50. · 5.43 Impact Factor
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Indian pediatrics 07/1999; 36(6):597-9. · 1.05 Impact Factor
