R Sharma

Intravenous pulse cyclophosphamide — a new regime for steroid-resistant minimal change nephrotic syndrome

The treatment of steroid-resistant minimal change nephrotic syndrome (MCNS) continues to pose a therapeutic challenge. We conducted a randomised prospective controlled trial to evaluate the efficacy of IV cyclophosphamide compared with oral cyclophosphamide in 13 children with biopsy-proven steroid-resistant MCNS. All 7 patients receiving IV cyclophosphamide achieved remission; this was sustained in 4 patients, while 3 relapsed. However, even these 3 patients subsequently became steroid sensitive. Of the 6 patients who received oral cyclophosphamide, 2 dropped out, 1 responded and 3 children continued to remain steroid resistant. The children who received IV cyclophosphamide had more sustained remissions, longer periods without proteinuria and fewer significant side effects; this was achieved at a lower cumulative dose.

Daily Peritoneal Dialysis Using a Surgically Placed Tenckhoff Catheter for Acute Renal Failure in Children

Thirty-one infants and children with acute failure were treated with peritoneal dialysis using a surgically placed Tenckhoff catheter. In 10 patients a peritoneal dialysis cycler was used, and 21 were dialyzed by the manual method. Initially, hourly exchanges were given for 24 to 48 h and, as the patients stabilized, 10 exchanges per day at 1-h intervals were given. The mean stabilization period was 36 +/- 8 h. The predialysis mean serum creatinine was 5.8 +/- 1.8 mg% and the serum creatinine while on daily dialysis was 2.8 +/- 1.1 mg%. Peritoneal dialysis succeeded in controlling metabolic abnormalities and improving fluid balance. All the catheters except one functioned immediately following insertion. Median duration of catheter placement for dialysis was 18 days (range 2 to 90). The incidence of peritonitis was 12.8%, and exit site infection was 6.4%. The infection rate was decreased when a cycler was used compared with the manual method (23.8% vs. 10.0%), though not statistically significant. Two patients developed hypothermia while being dialyzed via the manual method. To conclude, 10 daily peritoneal dialysis exchanges performed at 1-h intervals after initial stabilization using a surgically placed Tenckhoff catheter is an effective and safe mode of dialytic therapy for children with acute renal failure. Complications (infection and hypothermia) are reduced with the use of a cycler.

Early versus late-onset idiopathic focal segmental glomerulosclerosis.

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 ≤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.

ABO-incompatible renal transplantation in developing world - crossing the immunological (and mental) barrier

ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.

Paired kidney exchange transplantation: Maximizing the donor pool.

In the last decade, paired kidney exchange (PKE) transplantation has gained popularity worldwide as a viable alternative for end stage renal disease (ESRD) patients who have incompatible or sensitized donors. This study presents our experience with PKE transplantation and compares outcome between PKE and non-PKE renal transplant recipients. Between February 2010 and November 2013, 742 transplants were performed, of which 26 (3.5%) were PKE transplantations. All were two-way exchanges. PKE recipients were significantly older than non-PKE (46.73 ± 9.71 vs. 40.08 ± 13.36 years; P = 0.012) while donor ages were comparable. PKE patients had significantly higher number of HLA mismatches (5.03 ± 1.14 vs. 3.49 ± 1.57; P < 0.0001). After a median follow-up of 20 months (range: 3–47 months), there was no significant difference in patient survival (PKE 96.16% vs. non-PKE 96.65%; P = 0.596) and death censored graft survival (PKE 96.16% vs. non-PKE 96.37%; P = 1). Mean serum creatinine at 1 month and at last follow-up was lower in PKE versus non-PKE group (0.98 ± 0.33 vs. 1.3 ± 0.61 mg/dl; P = 0.008 and 0.96 ± 0.30 vs. 1.27 ± 0.57 mg/dl, P = 0.006, respectively). Biopsy proven acute rejection rate was 11.5% in PKE group and 16.89% in non-PKE patients (P = 0.6). To conclude, paired kidney donation is an excellent way of increasing the donor pool and needs to be promoted to overcome the shortage of suitable kidney in our country.

Renal transplantation across ABO barrier

In India, patients without a compatible blood group donor are usually excluded from renal transplantation. For young patients, it is a difficult therapeutic choice to stay on long-term dialysis. We describe the case of a 19-year-old male patient who had blood group O +ve and had no compatible donor in the family. His mother was B +ve and was willing to donate. The patient had an initial anti-B antibody titer of 1:512 and underwent antibody depletion with plasmapheresis (11 sessions) and intravenous immunoglobulin (IVIG) 100 mg/kg after every plasmapheresis. He also received rituximab 500 mg for 3 days prior to transplant and was induced with basiliximab. At the time of transplant, his anti-B titers were <1:8. Post-operatively, he required four sessions of plasmapheresis and IVIG as his titers rebounded to 1:64. The titers then spontaneously subsided to <1:16 and have stayed at the same level for 6 months post-transplant. The patient continues to have normal renal function with a creatinine of 1.4 mg/dl% and has had no episodes of rejection.

The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study.

Objective: Acute kidney injury (AKI) is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG), is not uncommon after off pump coronary bypass surgery (OPCAB). Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG) within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT) and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery) and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN) and risk injury failure loss end stage (RIFLE) criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05). Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it.

Early corticosteroid withdrawal regimen in a living donor kidney transplantation program.

Steroids have been the essential component of transplant immunosuppression. Recently, with availability of better immunosuppressive agents, many centers have started steroid free transplant with good success rates. We analyzed the outcomes of early corticosteroid withdrawal (CSW) protocol in our living donor kidney transplant programme. We included 73 patients on CSW protocol on basiliximab + tacrolimus and mycophenolate mofetil and compared them with 67 recipients on similar regimen with corticosteroids (CSs). CSW group received prednisolone 40 mg on day 1, which was stopped on day 5. Outcomes were evaluated in terms of acute rejection (AR), infections, new onset diabetes after transplant (NODAT), renal function and graft or patient loss. In CSW group, 15/73 (20.5%) patients developed AR, when compared to 5/67 (7.5%) in CS group, (P = 0.02). Biopsy proven acute rejection was seen in 12/72 (16.6%) in CSW group and 5/67 (7.5%) in CS (P = 0.1). One patient in CSW group developed antibody mediated rejection. NODAT was similar (9% in CS vs. 3.7% in CSW, P = 0.09), but infections were higher in CSW group (20.5% vs. 7.5%, P = 0.02). Mean serum creatinine was similar at 6 months (1.24 ± 0.6 in CS and 1.25 ± 0.3 in CSW, P = 0.9). Graft survival was 100% and 97% (P = 0.1) and patient survival was 98.6% and 98.5% (P = 0.9) in CSW and CS groups. Early corticosteroid withdrawal with basiliximab induction was associated with increased risk of AR but did not have any effect on short term graft and pateint survival.

Uncommon cause of fever in a pediatric kidney transplant recipient: Answers

A bone marrow and lymph node biopsy was undertaken. The lymph node biopsy showed granulomas and abundant intracellular yeast forms of Histoplasma (Fig. 1), and the bone marrow biopsy revealed hypocellularity, increased macrophages laden with Histoplasma and hemophagocytosis. Immunostaining of the glycoprotein CD68 (clone S14H12; Leica Biosytems, Wetzlar, Germany) confirmed the presence of many macrophages in the bone marrow, and Grocott’s special stain for Histoplasma showed that the yeast was residing within the reticuloendothelial cells (Fig. 2). Peripheral blood smear showed thrombocytopenia and reticulocytopenia with no evidence of the yeast. The results of liver function tests were normal. A urinary antigen test for Histoplasma, serum antiHistoplasma antibodies and soluble interleukin-2 receptor level could not be performed due to the unavailability of these diagnostics. A transplant biopsy was not done due to a deranged coagulation profile. Consequently renal histoplasmosis could not be ruled out. Based on the diagnosis of disseminated histoplasmosis, the patient was administered intravenous liposomal amphotericin B for 4 weeks, following which he was switched to itraconazole. After 2 months on itraconazole, the patient was switched to voriconazole. The doses of immunosuppressants were reduced to achieve a complete eradication of infection. He was kept on a dual immunosuppression regimen (tacrolimus level 4–6 ng/ml and prednisolone 7.5 mg), and his clinical condition improved and the pancytopenia resolved completely in the following weeks. The patient is currently in stable condition, with a creatinine level of 2.5 mg/dl and no symptoms.