Effects of Individualized Dialysate Sodium Prescription in Hemodialysis - Results from a Prospective Interventional Trial.

INTRODUCTION: Individualized dialysate sodium prescription does affect weight gain, blood pressure (BP), and intradialytic complications. A prospective interventional trial (Dialysate Individualised Sodium (DISO) trial) was conducted to study this issue in Indian patients. METHODS: Forty patients on thrice-weekly maintenance hemodialysis (HD) for at least 6 weeks were enrolled. The study was performed in two different phases. In the first phase, 12 consecutive HD sessions were done with a standard dialysate sodium concentration of 140 mEq/L. In the second phase, 12 consecutive HD sessions were done with dialysate sodium concentration set to individualized value (mean of pre-HD sodium concentration multiplied by Donnan coefficient of 0.95). Differences in pre- and post-HD sodium, interdialytic weight gain (IDWG), pre- and post-HD BP, thirst scores, and intradialytic adverse events during both phases were assessed. RESULTS: The mean age of patients was 45.65 years (24 males, 16 females). The mean serum pre-HD sodium level was 138.7 ± 1.7 meq/L in the standard phase and 138.2 ± 2.6meq/L in the individualized phase (P = 0.229). In the standard phase, the mean IDWG was 2.64 ± 1.56 kg and 2.13 ± 0.99 kg in the individualized phase (P = 0.008). The mean pre-HD systolic BP was 138 ± 18 mmHg and 134 ± 17 mmHg in the standard and individualized phases (P = 0.008). There was no difference in intradialytic symptoms, hypotensive episodes or requirement of interventions. Hypertension episodes occurred at a mean value of 2.2 and 1.2 in the standard and individualized phases, respectively (P = 0.010). CONCLUSION: The use of individualized dialysate sodium level is safe and results in lower IDWG, pre-HD systolic BP, and intradialytic hypertension in patients on HD.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft-Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland-Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

Hemostatic Abnormalities in Severe Renal Failure: Do They Bark or Bite?

Abnormal primary hemostasis is believed to be the most significant contributor to uremic bleeding. This study aimed to describe the prevalence and profile of primary and secondary hemostatic disorders in patients with chronic kidney disease (CKD) Stages 4 and 5 and to determine their association if any, with degree of uremia. Stages 4 and 5 predialysis CKD patients attending nephrology outpatient clinic were prospectively recruited and the following bleeding parameters were measured in all patients: platelet count, bleeding time (BT), Factor VIII assay, von Willebrand factor antigen (vWF:Ag), vWF:ristocetin cofactor activity (vWF:RCo), ratio of vWF:ristocetin cofactor activity to vWF antigen (vWF:RCo/vWF:Ag), prothrombin time (PT), and activated partial thromboplastin time (aPTT). Forty-five patients (80%, males) with a mean age of 39.4 years, 82% (n = 37) in Stage 5 CKD, were recruited for the study. The prevalence of thrombocytopenia was significantly higher among patients from West Bengal (15/26, 57.7%) compared to other study patients (2/19, 10.5%; P = 0.001); however, all had macrothrombocytes with normal BT, suggestive of the Harris syndrome. Factor VIII, vWF:Ag, vWF:RCo, vWF:RCo/vWF:Ag ratio, BT, PT, and aPTT were abnormal in 0 (0%), 0 (0%), 0 (0%), 4 (8.8%), 1 (2.2%), 7 (15.6%), and 5 (11.1%) patients, respectively. Except for thrombocytopenia, the prevalence of hemostatic abnormalities did not differ between CKD Stages 4 and 5. Hemostatic abnormalities are uncommon in Stages 4-5 CKD and except for thrombocytopenia, are not associated with degree of uremia. Constitutional macrothrombocytopenia is associated with normal BT even in CKD.

Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): a series from a tertiary care teaching hospital in South India.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease. This disease may be associated with elevated serum and tissue IgG4 levels. Early treatment prevents fibrosis and organ damage. We retrospectively studied the clinicopathologic correlation and outcome of treatment in IgG4-RD. This single-center retrospective study was done using electronic records of patients subjected to assay of serum IgG4 levels in our laboratory by nephelometry. There were 473 patients with suspected IgG4-RD. Of them, 41 patients fulfilled comprehensive diagnostic criteria for IgG4-RD and 432 had diseases other than IgG4-RD. Clinical and histopathological data including tissue IgG4/IgG ratio, other relevant laboratory findings as well as management data of 41 patients with IgG4-RD were analyzed. There were 29 males and 12 females with mean age of 44.1 ± 2.19 years. Thirteen patients had definite, 19 had probable and 9 had possible IgG4-RD. Male predominance, multiple organ involvement and IgG4 responder Index were significantly higher in definite IgG4-RD as compared to probable and possible IgG4-RD. Serum IgG4 level was elevated in 37 patients (90.2%). Glucocorticoids were used in 35 patients (85.4%) and second-line immunosuppressive agent in 23 patients (65.7%). Of the 21 patients on follow-up, 19 (90.7%) had clinical improvement at the first follow-up visit. Nine (90%) out of the ten patients who were assessed by IgG4 responder index, also had shown improved score with treatment. Patients with IgG4-RD in our series showed favorable responses to treatment with glucocorticoids and addition of steroid sparing immunosuppressive agents (mainly mycophenolate mofetil) helped successful tapering of steroids, while maintaining the improvement.

Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease.

Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India.

Adefovir nephrotoxicity in a renal allograft recipient.

Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN) were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

Immunoglobulin G4-related tubulointerstitial nephritis associated with interstitial pulmonary disease: Report of a case with review of literature.

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathological entity. Renal involvement is dominated by tubulointerstitial nephritis (TIN) with IgG4-positive plasma cells and fibrosis. IgG4-RD commonly affects middle-aged to elderly men with accompanying extra-renal lesions such as sialadenitis, lymphadenopathy, or type 1 autoimmune pancreatitis, all of which respond favorably to corticosteroid therapy. The disease burden of IgG4-related kidney disease (IgG4-RKD) in India remains largely underestimated. We report a case of IgG4-RKD manifesting as TIN associated with interstitial pulmonary disease, illustrating typical clinico-pathologic, serologic, immuno-histochemical, and ultrastructural features of this condition. In view of potential amelioration of renal dysfunction with appropriate therapy, the need for awareness of this condition and early diagnosis is highlighted.

Clinical outcomes of endovascularly managed iatrogenic renal hemorrhages.

OBJECTIVE: To evaluate the effectiveness of endovascular management in iatrogenic renal injuries with regard to clinical status on follow-up and requirements for repeat angiography and embolization. MATERIALS AND METHODS: This retrospective study included patients who were referred for endovascular management of significant hemorrhage following an iatrogenic injury. Data was recorded from the Picture Archiving and Communication system (PACS) and electronic medical records. The site and type of iatrogenic injury, imaging findings, treatment, angiography findings, embolization performed, clinical status on follow-up, and requirement for repeat embolization were recorded. The outcomes were clinical resolution, nephrectomy, or death. Clinical findings were recorded on follow-up visits to the clinic. Statistical analysis was performed using descriptive statistics. RESULTS: Seventy patients were included in this study between January 2000 and June 2012. A bleeding lesion (a pseudoaneurysm or arteriovenous fistula) was detected during the first angiogram in 55 patients (78.6%) and was selectively embolized. Fifteen required a second angiography as there was no clinical improvement and five required a third angiography. Overall, 66 patients (94.3%) showed complete resolution and 4 patients (5.7%) died. Three patients (4.3%) underwent nephrectomy for clinical stabilization even after embolization. There were no major complications. The two minor complications resolved spontaneously. CONCLUSIONS: Angiography and embolization is the treatment of choice in iatrogenic renal hemorrhage. Upto 20% of initial angiograms may not reveal the bleed and repeat angiography is required to identify a recurrent or unidentified bleed. The presence of multiple punctate bleeders on angiography suggests an enlarging subcapsular hematoma and requires preoperative embolization and nephrectomy.

Efficacy and safety of hepatitis C antiviral therapy in moderate and severe chronic kidney disease.

Hepatitis C virus (HCV) infection is an important cause of liver-related morbidity and mortality in patients with end-stage renal disease (ESRD). Though indicated, antiviral therapy adds to the existing financial burden and is poorly tolerated in these patients. We studied HCV treatment outcomes in patients with moderate and severe chronic kidney disease (CKD) between June 2010 and June 2012. Out of 46 patients with CKD, only 16 (genotype 1:6, 3:9, indeterminate 1) received interferon treatment (conventional 9, pegylated 7; with low-dose ribavirin 5). End of treatment response was achieved in 50 % and sustained viral response in 44 %. Adverse effects such as tuberculosis, anemia, and cardiac failure resulting in discontinuation of therapy were seen in three. The dropout rate was 38 %. Though interferon therapy was efficacious and safe, it was received by only 35 % of patients with CKD. We suggest that antiviral therapy be offered under close monitoring in the absence of contraindications in patients with moderate and severe CKD.

Profile of incident chronic kidney disease related-mineral bone disorders in chronic kidney disease Stage 4 and 5: A hospital based cross-sectional survey.

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD patients. We aimed to study the clinical, biochemical and extra skeletal manifestations of untreated CKD-MBD in pre-dialysis Stage 4 and 5 CKD patients attending nephrology out-patient clinic at a tertiary care hospital in South India. A hospital based cross-sectional survey including, demographic profile, history of CKD-MBD symptoms, measurement of serum calcium, phosphate, parathyroid hormone, 25 hydroxy vitamin D (25(OH) D) and alkaline phosphatase; lateral abdominal X-rays for abdominal aortic calcification (AAC) and echocardiography for valvular calcification (VC) was carried out. Of the 710 patients surveyed, 45% had no CKD-MBD related symptom. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism (>150 pg/mL) and 25(OH) D levels <30 ng/mL was 66.3%, 59%, 89.3% and 74.7% respectively. Echocardiography was carried out in 471 patients; 96% of whom had VC (calcification score ≥1). Patients with VC were older and had lower 25(OH) D levels than those without. Lateral abdominal X-rays were obtained in 558 patients, 6.8% of whom were found to have AAC, which was associated with older age. Indian patients with incident CKD-MBD have a high prevalence of hypocalcemia, 25(OH) D deficiency and VC even prior to initiating dialysis while AAC does not appear to be common. The association between 25(OH) D deficiency and VC needs further exploration.

Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression?

Posterior reversible encephalopathy syndrome (PRES) is an uncommon post-renal transplant complication. We report a 16-year-old boy who had an acute cellular rejection immediate post-transplant and was given intravenous methylprednisolone along with an increase in tacrolimus dose. He was diagnosed to have PRES based on clinical and radiological features within 6 h of intensified immunosuppression. This is an unusual case report of successfully managing PRES with continuation of the intensified immunosuppression as warranted by the clinical situation, along with aggressive blood pressure control. After 6 weeks, magnetic resonance imaging showed complete resolution of lesions. He has good graft function and no residual neurological deficits while on small doses of three antihypertensives, 12 months after transplantation.

Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature.

Emphysematous pyelonephritis (EPN) is a rare occurrence in renal allografts. An aggressive approach resulting in transplant nephrectomy is viewed as the standard of care. Over the recent years, treatment with percutaneous drainage (PCD) of the renal and perinephric collections and appropriate antibiotics has been reported with good success in lesser grades of this infection. Only 4 cases of extensive EPN disease with Escherichia coli, treated with conservative management, are reported in the English-language literature. We present a case of severe EPN caused by Klebsiella pneumoniae, successfully managed with early PCD, and propose a step-up strategy aimed toward graft preservation.

Successful renal transplantation following treatment of Aspergillus terreus peritonitis in a continuous ambulatory peritoneal dialysis patient.

Peritoneal dialysis (PD) related peritonitis caused by fungi is a potentially life-threatening complication. It diminishes prospects of continuing PD. We report a patient with Aspergillus terreus peritonitis treated successfully with catheter removal and antifungal therapy and subsequently had a live-related renal transplantation. There was no recurrence of the infection in 3 years of follow-up.

Medical and non-medical factors that affect voluntary living-related kidney donation: A single-center study.

The aim was to evaluate the patients with chronic kidney disease stage 5 (CKD 5) and their prospective renal transplant donors with regard to their renal replacement choices, and to assess the medical and non-medical factors that affect living-related renal donor selection. Over 24 months, consecutive patients with CKD 5 and their relatives were interviewed at presentation. Reasons for the choice of modality were analyzed; the prospective recipients and their donors were again interviewed separately and the medical and nonmedical factors that affected the donor selection were determined. A total of 1257 patients were enrolled. Conservative therapy, maintenance dialysis, and renal transplantation were chosen by 513 (40.8%), 320 (25.5%), and 424 (33.7%) patients, respectively. Only socioeconomic status affected the modality chosen. The age, gender, and donor availability did not emerge as significant factors. Patients or donors were likely to withdraw from transplant evaluation due to the absence of a voluntary donor, presence of a male donor, coercion not to donate, and the absence of reimbursement. The commonest cause of rejection of a donor was blood group incompatibility (45.8%), followed by diabetes mellitus (DM) or risk of DM (24%), renal disease (5.9%), hypertension (5.5%), and persistent cross-match positivity (5.1%). To improve donation rates, the donor's spouse should be involved in the early stages of donor evaluation, financial support for the recipient has to be improved, and the apprehensions about complications of nephrectomy among the donors need to be alleyed. Male donors are at increased risk of leaving the program in the evaluation phase.

Pediatric renal transplantation--a single center experience of 15 yr from India.

Renal transplantation is the optimal treatment for children with ESRD. We undertook this study to establish the outcome of pediatric renal transplants in a resource-constrained environment in a developing country. A retrospective analysis on 90 pediatric renal transplants (age at transplant 2 rejection episodes (p = 0.05), while sepsis (p = 0.01) was the most important contributor to patient loss. Pediatric renal transplantation in India can be accomplished successfully. The graft and patient survival in our study, the largest from India, is comparable to those published from developed countries and is encouraging given the limited resources.