Renal Manifestations in Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired chronic disorder characterized by a triad of clinical features - hemolytic anemia, pancytopenia, and thrombosis. Not many reports of renal involvement in PNH are available in literature. We present a case series of PNH with renal involvement. We present the data of PNH patients who attended to Departments of General Medicine and Nephrology at a government-run tertiary care institute in South India. The diagnosis of PNH in these patients during initial phase, between 1998 and 2004 was based on sucrose lysis and Ham's test. After 2004, the diagnosis was based on flow cytometry to detect CD59 (membrane inhibitor of reactive lysis), a glycoprotein, and CD55 (decay accelerating factor) in regulation of complement action. The patient data were collected from 1998 to 2014. There were 14 patients of PNH in this period. The mean age was 37 years and the range was 16-68 years. There were eight females. Acute kidney injury (AKI) was noted in six patients. Dialysis was performed in four of them. The mean serum creatinine and urea at the initiation of dialysis were 5.4 ± 0.6 and 64.1 ± 6.1 mg/dl, respectively. The median number of hemodialysis sessions done was four. Renal biopsy was done in four patients. In three patients, the urinalysis and serum chemistry were suggestive of Fanconi syndrome. In our patients, three renal manifestations of PNH were identified. They were AKI, renal vessel thrombosis, and Fanconi syndrome. Chronic renal failure was not identified.

Identification of urinary proteins potentially associated with diabetic kidney disease.

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Although several parameters are used to evaluate renal damage, in many instances, there is no pathological change until damage is already advanced. Mass spectrometry-based proteomics is a novel tool to identify newer diagnostic markers. To identify urinary proteins associated with renal complications in diabetes, we collected urine samples from 10 type 2 diabetes patients each with normoalbuminuria, micro- and macro-albuminuria and compared their urinary proteome with that of 10 healthy individuals. Urinary proteins were concentrated, depleted of albumin and five other abundant plasma proteins and in-gel trypsin digested after prefractionation on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The peptides were analyzed using a nanoflow reverse phase liquid chromatography system coupled to linear trap quadrupole-Orbitrap mass spectrometer. We identified large number of proteins in each group, of which many were exclusively present in individual patient groups. A total of 53 proteins were common in all patients but were absent in the controls. The majority of the proteins were functionally binding, biologically involved in metabolic processes, and showed enrichment of alternative complement and blood coagulation pathways. In addition to identifying reported proteins such as α2-HS-glycoprotein and Vitamin D binding protein, we detected novel proteins such as CD59, extracellular matrix protein 1 (ECM1), factor H, and myoglobin in the urine of macroalbuminuria patients. ECM1 and factor H are known to influence mesangial cell proliferation, and CD59 causes microvascular damage by influencing membrane attack complex deposition, suggestive their biological relevance to DN. Thus, we have developed a proteome database where various proteins exclusively present in the patients may be further investigated for their role as stage-specific markers and possible therapeutic targets.

Focal and segmental glomerulosclerosis: does prognosis vary with the variants?

Focal and segmental glomerulosclerosis (FSGS) is a clinicopathological entity. The following five FSGS variants: Collapsing, cellular, glomerular tip, peri-hilar and not otherwise specified (NOS) are recognized, which may have prognostic value. The aim of this study was to highlight the clinical course and outcome in the different pathological variants of FSGS and to evaluate the predictive risk factors of end-stage renal disease (ESRD). It was a retrospective analysis of biopsy-proven primary FSGS patients who presented over a period of three years. The data were collected from the clinical and biopsy records of the Nephrology Unit. There were 116 patients with biopsy-proven FSGS. The frequency of occurrence of FSGS among all cases of the nephrotic syndrome seen in our unit was 35.47%. NOS was the most common pathological variant (62.2%), followed by peri-hilar (11.2%), cellular (9.4%) and glomerular tip (7.7%), and the least common variant was collapsing (4.3%). Majority of patients with collapsing, NOS and glomerular tip variants had nephrotic range proteinuria. However, the amount of proteinuria was highest in the glomerular tip and collapsing variants. A higher percentage of patients with the collapsing and cellular variants had renal failure at the time of presentation. A higher rate of tubular and interstitial changes was seen in the collapsing and cellular variants. The collapsing and cellular variants showed lower response rate and higher rates of ESRD, while the glomerular tip lesion had the highest remission rate and the lowest rate of ESRD. Poor prognostic factors for ESRD in FSGS were initial renal insufficiency, severe tubulo-interstitial change, initial nonresponsiveness to steroids and collapsing histopathological variant. Our study suggests that histopathological classification of FSGS is of paramount importance in the management and in predicting the prognosis.

Embolic occlusion of arteriovenous fistula due to infective endocarditis.

A 45-year-old male on maintenance hemodialysis through right radio cephalic arteriovenous fistula (AVF) also had mitral regurgitation. He presented with fever and chills of 2 days duration along with pain and swelling at median cubital fossa of right upper limb. Local examination revealed warmth, redness, and tenderness at median cubital fossa. AVF thrill was absent. Echocardiography revealed vegetations on the mitral valve. An extensive search of literature did not reveal an instance of embolic occlusion of AVF due to vegetations of infective endocarditis.

Membranous nephropathy superimposed on Churg-Strauss syndrome.

The association of membranous nephropathy with Churg-Strauss syndrome is not widely reported. We present a patient with myeloperioxidase-perinuclear antineutrophilic cytoplasmic antibody (MPO-pANCA)-positive necrotizing and crescentic glomerulonephritis who later developed membranous nephropathy.

Reinitiation of peritoneal dialysis after catheter removal for refractory peritonitis.

AIM: A high proportion of patients whose catheters are removed are unable to successfully reinitiate peritoneal dialysis (PD) due to irreversible peritoneal injury or to decisions made by the patient or the nephrologist for different and often empiric reasons. The present study examined the outcomes of patients reinitiated on PD after peritonitis. METHODS: We reviewed all patients with end-stage renal disease who were initiated on continuous ambulatory peritoneal dialysis at our Institute in south India between 1998 and 2012, identifying those in whom the catheter was removed and the cases where PD was reinitiated, analysing the reasons and outcome. We compared data of patients who could be reinitiated on PD with those who could not be reinitiated and also data of patients who successfully continued PD after reinitiation with those who suffered technique failure. RESULTS: Peritoneal dialysis was reinitiated in 31 (19.4%) of 159 patients whose catheter was removed owing to refractory peritonitis, including after an episode of Pseudomonas aeruginosa and fungal peritonitis. Some patients had the catheter placed for a third time. No significant difference was found between patients who reinitiated PD vs. did not, or between those who were successful in reinitiating PD vs. unsuccessful. CONCLUSION: Notwithstanding the small cohort size, the present study demonstrates that reinitiating PD is feasible in a developing country, and also that reinitiation of PD is possible after an episode of P. aeruginosa and fungal peritonitis. However, future studies in a larger patient cohort and assessing dialysis adequacy are required to confirm and extend our findings.

Granulomatous interstitial nephritis: Our experience of 14 patients.

Granulomatous interstitial nephritis (GIN) is a rare condition. Drugs, infections, immune processes, and foreign body reaction are the main causes. We identified a total of 14 patients with GIN during a period of 13 years in 2798 renal biopsies. There were 8 males and 6 females in the age range of 20-70 (mean 35 ± 12) years. The serum creatinine at presentation was 6.7 ± 3.8 (range: 2.3-14.7) mg/dl. In nine patients tuberculosis was the causative agent. Drugs (n = 2) and Wegener's granulomatosis (n = 1) were other etiologies. Systemic lupus erythematosis (SLE) and Immunoglobulin A nephropathy (IgAN) were seen in one patient each. Patients with tuberculosis were treated with antituberculous therapy and three of them improved. Four out of six patients who required dialysis at presentation remained dialysis dependent, one of whom underwent renal transplantation. Two patients progressed to end stage renal disease after 7 years and 9 years each. The patients with drug induced GIN had improvement in renal function after prednisolone treatment. Patients with SLE, and Wegener's granulomatosis responded to immunosuppression. Patient with IgAN was on conservative management. Finally, six patients were on conservative management for chronic renal failure.

A 2-year follow-up study of patients on automated peritoneal dialysis.

Automated peritoneal dialysis (APD) is increasingly being used for the treatment of end stage renal disease. We present our experience of APD at a government run tertiary care institute. APD was initiated for 22 patients between 2002 and 2010. On comparing APD and continuous ambulatory peritoneal dialysis (CAPD) patients, no difference in patient survival and technique survival was observed. CAPD patients had higher number of peritonitis episodes, greater decline in the serum albumin and a greater number of patients failed to achieve adequacy targets compared to APD.

Tuberculosis in haemodialysis patients: A single centre experience.

We prospectively followed-up new patients of tuberculosis while on maintenance hemodialysis at a State Government-run tertiary care institute. Between 2000 and 2010, 1237 new patients were initiated on maintainence hemodialysis. The number of patients diagnosed with tuberculosis after initiation of hemodialysis was 131 (10.5% of 1237). The age was 46.4 ± 10.4 (range 8-85) years and there were 90 (68.7%) males. The number of patients diagnosed with tuberculosis on the basis of organ involvement were: Pulmonary-60, pleural effusion-31, lymph node-21, meningitis-8, pericardial effusion-7, peritoneum-2, latent tuberculosis-2. The incidence of tuberculosis in hemodialysis was found to be 105.9 per 1000 patient years. Male gender, diabetes mellitus, past history of tuberculosis, mining as an occupation, low serum albumin, and duration of hemodialysis more than 24 months, and unemployment were found to be significant risk-factors on univariate analysis.

Fulminant hepatic failure following marijuana drug abuse: Molecular adsorbent recirculation system therapy.

Marijuana is used for psychoactive and recreational purpose. We report a case of fulminant hepatic failure following marijuana drug abuse who recovered following artificial support systems for acute liver failure. There is no published literature of management of marijuana intoxication with molecular adsorbent recirculation system (MARS). MARS is effective and safe in patients with fulminant hepatic failure following marijuana intoxication.

Allopurinol for prevention of progression of kidney disease with hyperuricemia.

Hyperuricemia is associated with hypertension and progressive chronic renal disease. This is a retrospective cohort study in chronic kidney disease (CKD) patients with hyperuricemia from 1998 to 2008. Patients were divided into two groups: treatment group who received allopurinol in a dose of 100 mg/day and the other group remained untreated. Clinical, hematologic, biochemical parameters and outcome were measured at baseline and 6 months, 1 year, and 2 years of treatment. A total of 183 patients were enrolled. Mean age of the allopurinol group was 50.15 ± 14.42 years and control group was 53.23 ± 13.86 years. Male-female ratios were 2.57:1 and 2.21:1 for the treatment and control groups, respectively. Baseline characteristics and the laboratory parameters were similar in both groups. Patients who received allopurinol had lower blood pressure at 6 months, 1 year, and 2 years when compared to baseline. There was a significant decrease in the serum uric acid (UA) levels in the treatment group at the end of 6 months, 1 year, and 2 years with respect to base line. An inverse correlation as noted between serum UA levels and the estimated glomerular filtration rate at 6 months, 1 year, and 2 years. Allopurinol treatment decreases blood UA levels and is associated with better blood pressure control and decreased progression of renal disease in CKD patients with hyperuricemia.

Rhabdomyolysis induced acute renal failure secondary to statins.

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation. We report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins.

The effect of L-arginine on arterial stiffness and oxidative stress in chronic kidney disease.

Chronic kidney disease (CKD) is a growing problem worldwide. The disproportionate increase in the burden of cardiovascular disease in patients with CKD may be significantly contributed by nontraditional risk factors. Increased arterial stiffness has been recognized as an important player in contributing to this morbidity and mortality. The aim of this study was to report the effect of L-arginine on arterial stiffness and oxidative stress in patients with CKD. Thirty patients with stage II to IV CKD were administered 9 g of L- arginine per day orally for a period of 12 weeks. The parameters evaluated at baseline, at 8 weeks, and at the end of 12 weeks were serum nitric oxide (NO), carotid.femoral pulse wave velocity (cf PWV), and radial artery pulse wave analysis which included aortic augmentation pressure (AP), aortic augmentation index (AIx), aortic augmentation index at heart rate of 75 bpm, subendocardial viability ratio, radial pressures, and central aortic pressure. Serum levels of NO and malondialdehyde (MDA) were estimated at baseline and at the end of 12 weeks. The control group was composed of age- and sex-matched healthy individuals. Twenty-five patients completed the study. Two patients were lost to follow.up; three patients developed adverse events and were excluded. Baseline NO levels were low (13.55 ± 7.49 µM/L) in all the subjects. Administration of L-arginine resulted in improvement in the carotid-radial PWV (m/s) (10.08 ± 1.72 at baseline to 8.56 ± 1.16 by 12 weeks; P < 0.001), cf PWV (m/s) (13.06 ± 2.65 at baseline to 10.62 ± 1.93 at 12 weeks; P < 0.001), Aortic Augmentation Index (%) (32 ± 10.34 at baseline to 17.84 ± 8.05 at 12 weeks; P < 0.001), aortic augmentation pressure (mm of Hg) (14.03 ± 6.53 at baseline to 7.12 ± 3.85 at 12 weeks; P < 0.001), and NO (µM/L) (13.55 ± 7.49 at baseline to 30.22 ± 9.8 at 12 weeks; P < 0.001). There was no significant change in the levels of MDA (nanomol/ml) (20.0 ± 10.14 at baseline and 19.16 ± 9.36 at 12 weeks; P = ns). In conclusion, PWV, an indicator of arterial stiffness, is greatly increased even in the early stages of CKD. Supplementation of L-arginine is a safe, well-tolerated, and effective way of improving endothelial dysfunction in patients with CKD.

Nondiabetic kidney disease in type 2 diabetic patients: A single center experience.

Nondiabetic renal disease (NDRD) is seen as a cause of proteinuria and renal failure in type 2 diabetes mellitus (DM). The clinical differences between NDRD and diabetic glomerulosclerosis (DGS) are not clear. This study was done to find the spectrum of NDRD in type 2 DM patients and differences in clinical profile between NDRD and DGS patients. Data of patients with type 2 DM who underwent renal biopsy in this institute from 1990 to 2008 were analyzed retrospectively. Patients were categorized as isolated NDRD, NDRD with DGS, and isolated DGS. A total of 75 patients were included. Mean age was 45 ± 10.2 years, male to female ratio was 3.1 : 1, median duration of DM was 12 months (range, 1 year-15 years), proteinuria was 4.2 ± 3.4 g/day, and serum creatinine was 4.3 ± 3.9 mg/dl. Hypertension was observed in 63 (84%) cases and microscopic hematuria in 24 (32%) cases. Nephrotic syndrome (38.7%) was the commonest clinical presentation. Forty-eight (64%) cases had NDRD and 27 (36%) had DGS. The commonest NDRD was minimal change disease (12.5%). Three (6.3%) patients had lupus nephritis. Tubulointerstitial nephritis has been observed in 10.4% patients. No significant differences between NDRD and DGS patients were found except hypertension which was significantly high in the DGS group. Acute kidney injury and nephritic syndrome were not observed in the DGS group. In conclusion, the incidence of biopsy-proven NDRD in type 2 DM in this study was high. Kidney biopsy aided in the detection of NDRD in clinically suspected patients.