Sanjeev Gulati

Changing trends of histopathology in childhood nephrotic syndrome

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.

Prognosis of acute renal failure in children: a multivariate analysis

Abstract. Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P <0.05) and associated with cardiac surgery (90.9%, P <0.01). Anuria (67.6% vs. 43.5%, P <0.05), need for dialysis (85.3% vs. 56.5%, P <0.05), neurological complications (50% vs. 6.3%, P <0.01), and respiratory complications (35.2% vs. 2.1%, P <0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors.

Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease

BACKGROUND Children with idiopathic nephrotic syndrome (INS) may be at risk for metabolic bone disease (MBD) because of biochemical derangements caused by the renal disease, as well as steroid therapy. No large study to date has shown conclusively that these children are prone to MBD. METHODS We prospectively studied 100 consecutive children with INS for clinical, biochemical, and radiological evidence of MBD. These children were treated with prednisone as follows: initial episode, prednisone, 60 mg/m2/d for 6 weeks, followed by 40 mg/m2 on alternate days for 6 weeks. Relapses were treated with 60 mg/m2/d until remission for 3 days, followed by 40 mg on alternate days for 4 weeks and tapered by 10 mg/m2/wk. Osteoporosis is defined as a bone mineral density (BMD) value evaluated by dual-energy X-linked absorptiometry of the lumbar spine of a z score of 2.5 SDs less than the mean. Univariate and multivariate analyses were performed to analyze for factors predictive of low BMD z score. Children were divided into two groups: those who had received repeated courses of steroid therapy (group II: frequent relapsers (FRs), steroid dependent (SD), or steroid nonresponders (SNRs) versus those who had received infrequent courses (group I: infrequent relapsers). RESULTS Twenty-two of 100 children (22%) had osteoporosis. Comparing clinical features, we observed that 6 of 70 children in group II were symptomatic (hypocalcemic signs) compared with none of 30 children in group I (P = 0.10). However, children in group II had significantly lower mean BMD z scores compared with group I (-1.65 +/- 1.35 versus -1.08 +/- 1.0; P = 0.01). Also, 20 of 70 children in group II had osteoporosis compared with 2 of 30 children in group I (P = 0.012). Children in group II had been administered significantly greater doses of steroids compared with group I (P < 0.00001). On multivariate analysis, factors predictive of a low BMD score were older age at onset (P = 0.000), lower total calcium intake (P = 0.000), and greater cumulative steroid dose (P = 0.005). CONCLUSION Children with INS are at risk for low bone mass, especially those administered higher doses of steroids (FRs, SD, or SNRs). These children should undergo regular BMD evaluations, and appropriate therapeutic interventions should be planned.

Etiology and outcome of chronic renal failure in Indian children

Abstract A prospective analysis of all new pediatric cases of chronic renal failure (CRF) was performed at our hospital over a 1-year period. The diagnosis of CRF was based on serum creatinine >2 mg/dl with supportive clinical, laboratory, and radiological findings. There were a total of 48 patients with CRF with a median age of 13 years (range 10 days to 16 years). The causes of CRF included glomerulonephritis (37.5%), obstruction and interstitial (52%), hereditary (6.3%), and undetermined (4.2%). Patients were symptomatic for a mean of 33.2 months (range 10 days to 11 years) at presentation. Eight patients (16.7%) had acute reversible deterioration of renal function at presentation. This was due to accelerated hypertension in 2, infection in 3, volume depletion in 2, and nonsteroidal antiinflammatory drugs in 1 patient. At presentation, 22 (46%) children had mild to moderate renal failure and 26 (54%) had end-stage renal disease. Twenty-one children (43.7%) had associated illness at presentation. Mean follow-up was 22.9 weeks (range 2–126 weeks). At the end of the study period, 10 (21%) patients were on conservative treatment, 7 (14.6%) on maintenance dialysis, 8 (16.7%) patients had functioning allografts, 4 (8.3%) patients had died, and 19 (39.6%) opted against further therapy. We conclude that CRF in Indian children carries a poor prognosis due to late referral and the limited availability and high cost of renal replacement therapy.

Chronic hepatitis C virus infection in renal transplant: treatment and outcome

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.

Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection

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).

Do current recommendations for kidney biopsy in nephrotic syndrome need modifications

Abstract The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness (P=0.02) than with histo- pathology (P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1–16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy.

Role of Vascular Access as a Risk Factor for Infections in Hemodialysis

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.

ETIOLOGY, PROGNOSIS, AND OUTCOME OF POST-OPERATIVE ACUTE RENAL FAILURE

A Multivariate analysis was done in all patients who developed post operative ARF, during the period 1990–1995 to determine the etiological spectrum and to identify various variables affecting the outcome. Of 140 patients (110 operated at SGPGI and 30 operated outside) 116 underwent elective surgery. The different types of surgery leading to ARF were urosurgery (3.5%), open heart surgery (32.9%), gastrosurgery (16.4%), pancreatic surgery (9.3%), obstetrical surgery (3.6%) and others (2.8%). The incidence of ARF in SGPGI patients was highest in pancreatic surgery group (8.2%) followed by open heart surgery (3%). The different etiological factors responsible for ARF were perioperative hypotension (67.1%), sepsis (63.6%) and exposure to nephrotoxic drugs (29.3%). Sixty-four patients (45.7%) required dialysis. The overall mortality was 45% The mortality was highest in patients who underwent open heart surgery (89.1%) followed by pancreatic surgery (84.6%). The factors associated with high mortality, other than the type of surgery, were preoperative hypotension (p <0.05), oliguria (p <0.01), need for dialysis (p <0.05) and multiorgan failure (p <0.001). AM following emergency surgery had poor outcome, though not statistically significant. Perioperative sepsis (p <0.05) and preoperative use of aminoglycoside (p <0.05) were significantly higher in patients operated outside SGPGI. This was associated with higher incidence of ARF. Thus we conclude that presence of multiorgan failure, oligoanuria, preoperative hypotension and need far dialysis are poor prognostic markers in ARF following surgery.

Steroid response pattern in Indian children with nephrotic syndrome

Gulati S, Kher V, Sharma RK, Gupta A. Steroid response pattern in Indian children with nephrotic syndrome. Acta Pædiatr 1994;83:530–3. Stockholm. ISSN 08033–5253