Sk Agarwal

Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study.

There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15–67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 106 copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.

Liver biopsy in patients on hemodialysis with hepatitis C virus infection: An important tool.

Hepatitis C virus (HCV) infection is commonest blood borne infection amongst hemodialysis patients. Still, there is paucity of data on liver biopsy in these patients. Our center is doing regular liver biopsy in these patients and thus thought of sharing our experience. In this retrospective study, all patients with HCV infection on hemodialysis were subjected to liver biopsy. Serum bilirubin, liver enzyme, HCV-PCR, genotype and viral load measurement were done in all. Biopsy specimen was stained with H and E, Periodic Acid Schiff, Gomori Stain, Masson Trichrome and Perls Stain. International Working Group scoring system of Ishak et al. was used for Grading and Staging. Of the 270 liver biopsies, mean age of patients was 34.05 ± 10.28 years and 233 (85.3%) were males. Mean duration of hemodialysis was 10.9 ± 7.4 months while of known HCV infection was 5.2 ± 4.0 months. Genotype 3 was commonest followed by 1. All had normal bilirubin and 64 (23.1%) had normal ALT. In 37 (13.3%) patients anti-HCV was not detectable. Mean histology grade was 4.03 ± 1.65 (1-10) and stage was 0.75 ± 0.98 (0-3). Only one patient had cirrhosis on histology. Associated hemosiderosis was seen 10 patients. Only minor complications were observed with no mortality. In conclusion, our study shows that in one-fourth patients with active liver disease, liver enzymes are persistently normal in patients on hemodialysis. Further, carefully performed liver biopsy is reasonably safe procedure though some patients do have non-fatal complications. Liver biopsy helps in assessing disease activity, which otherwise cannot be assessed. Histological grade and stage in these patients is usually mild and cirrhosis is rare. Till such time other non-invasive test is validated, liver biopsy will remain an important test in these patients.

Sequential, autologous hematopoietic stem cell transplant followed by renal transplant in multiple myeloma

A 30-year-old female was symptomatic with headache, fatigue, and weakness since October 2011 and was told to have anemia. In January 2012, she was admitted outside with pulmonary edema. Investigations revealed advanced azotemia, anemia, and hypercalcemia. Urine showed 2 + proteins and 30–35 red blood cells. There was no history of oral ulcers, rash, Raynauds phenomenon, or hemoptysis. She was evaluated for causes of rapidly progressive “renal failure.” Hemolytic work-up; antinuclear antibody, double-stranded DNA, and anti-neutrophil cytoplasmic antibody were negative. Kidney biopsy was done and interpreted as acute interstitial nephritis with hyaline casts. She was started on hemodialysis and treated with steroids and cyclophosphamide. She came to our institute in January 2012. Investigations showed evidence of paraproteinemia with kappa restriction. Bone marrow showed 15% plasma cells. Kidney biopsy was reviewed and was diagnostic of cast nephropathy. She was treated with 6 monthly cycles of dexamethasone and bortezomib. She achieved complete remission in July 2012. Maintenance doses of bortezomib were continued until May 2014. Autologous bone marrow transplantation was performed on June 06, 2014. Monthly, bortezomib was continued till April 2015. Subsequently, workup for renal transplantation was started with her father as her donor. Test for sensitization was negative. Renal transplantation was done on January 1, 2016, with prednisolone, mycophenolate, and tacrolimus. She achieved a serum creatinine of 0.6 mg% on the 4th postoperative day. Thereafter, she continues to remain stable.

Comparison of outcomes between surgically placed and percutaneously placed peritoneal dialysis catheters: A retrospective study

There is lack of adequate data on comparison of outcomes between percutaneously placed peritoneal dialysis (PD) catheters inserted by nephrologists and PD catheters placed by surgeons. The aim of this study is to retrospectively analyze the outcomes of PD catheters inserted by surgeons (by open surgical or laparoscopic technique) and compare them with those inserted by nephrologists among ESRD patients who underwent elective PD catheter insertions between January 2009 and December 2012. The primary outcome measure was the proportion of catheters removed because of primary nonfunction. The secondary outcome measures were catheter survival, patient survival, and incidence of complications of catheter insertion. A total of 143 PD catheter insertions (88 by surgeons and 55 by nephrologists) performed in 132 patients were considered for the analysis. The primary nonfunction rate of PD catheter insertions in both groups was comparable (18.2% and 7.3%, P = 0.08). Break-in period was shorter in Group N (p = <0.001). No differences were noted in patient or catheter survival. Percutaneously placed PD catheters performed by nephrologists have comparable outcomes with surgically placed PD catheters among selected cases and have the advantage of lower costs, avoidance of operation theater scheduling issues, smaller incision length, and shorter break-in period. Therefore, more nephrologists should acquire the expertise on percutaneous PD catheter placement as it leads to lesser waiting times and better utilization of PD.

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP) was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP <140/90 mmHg. Serial amlodipine levels were estimated in 16 patients; metoprolol and prazosin in four patients each. Drug levels declined by >50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001). Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46%) patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

Familial Pure Gonadal Dysgenesis with 46, XY Karyotype in Three Siblings and Gonadoblastoma in the Youngest Sibling

Abstract The occurrence of gonadoblastoma in XY phenotypic females has been well documented. This condition may rarely present in a familial form. In this present study, we present a family of 5 siblings born of non-consanguineous parents. Three sisters (age 13, 15 and 17 years) with XY karyotype presented with complaints of primary amenorrhoea. They had a normal female phenotype. The younger two brothers were apparently normal. All the three affected siblings have undergone laparoscopic removal of the gonads. The histopathology of gonads in the elder sibling (II 1) revealed ovarian stroma along with rete testes like elements. Bilateral tubes and the gonads of the younger sibling (II 2) showed fallopian tubes (both sides) and a small portion of ovarian stroma. No focus of gonadoblastoma was identified in these two elder siblings. Histopathology of the youngest sibling (II 3) revealed presence of bilateral gonadoblastoma. The occurrence of gonadoblastoma in the youngest sibling of 3 affected XY siblings is unusual.