Membranous nephropathy and granulomatous interstitial nephritis due to tuberculosis.

Tuberculous involvement of the genitourinary tract is well reported in the literature. However, reports of glomerular lesions of the kidney due to tuberculosis are rare. Tuberculosis has been identified as the most common infectious cause of granulomatous interstitial nephritis (GIN). We report a 23-year-old female patient with a membranous nephropathy and GIN due to tuberculosis. She presented with renal failure and nephrotic-range proteinuria, both of which resolved with the treatment of tuberculosis. There is only one report, from Japan, of a patient with membranous nephropathy and tuberculous granulomatous nephritis. Our patient is the second with tuberculous GIN and membranous nephropathy. In our patient, the close temporal relationship between the infection and glomerulonephritis, an ulcerated tuberculin skin test, the response to the treatment and the absence of any other systemic disease that might cause the glomerulonephritis suggested an association between tuberculosis and membranous nephropathy. However, a causal association can only be speculation, because membranous nephropathy could remit spontaneously. It is also possible that it might relapse at a later date when the tuberculosis is inactive. Therefore, the association might be either coincidental or causal, and could become clearer as similar patients are reported.

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.

Pharmacokinetics and pharmacodynamics of cisapride in patients undergoing hemodialysis.

Twenty-two patients who were receiving hemodialysis were studied in three groups of eight subjects each to assess the pharmacokinetics during the dialysis-free interval and during hemodialysis treatment and to assess the pharmacodynamics of cisapride. Cisapride and its metabolite norcisapride were measured by use of HPLC and gas chromatography, respectively. The pharmacodynamic effect of cisapride was measured by means of radionuclide gastric emptying. After a single oral dose of 20 mg the terminal half-life of cisapride was 9.6 +/- 3.3 hours, the volume of distribution was 4.8 +/- 3.3 L/kg, the total oral plasma clearance was 380 +/- 161 ml/min, the area under the curve was 1024 +/- 447 ng.hr/ml (mean +/- SD). Norcisapride only could be detected in the dialysate (0.36 +/- 0.067 mg) and was eliminated by a hemodialysis clearance of 34.7 +/- 7.9 ml/min. Cisapride reduced gastric retention from 77.6% +/- 21.1% to 43.7% +/- 18.2% of maximum filling (40 minutes after meals) and normalized the abnormal gastric emptying time in patients receiving dialysis. Cisapride dosage adjustment or substitution after hemodialysis is not necessary.

Oxidative stress in haemodialysis--intradialytic changes.

Oxidative stress is likely to be involved in the development of complications due to haemodialysis. Though there is evidence for production of oxygen free radicals during haemodialysis, reports on net oxidative imbalance due to a single dialysis session are conflicting. Hence, a time-course analysis of changes in lipid peroxides (LPO) along with antioxidant enzymes and vitamins was carried out. Hourly changes in LPO and antioxidants were studied during a first-use cuprophan membrane and acetate dialysis in 20 patients on regular haemodialysis treatment. Data were corrected for haemoconcentration and standardised to measure the rate of change before statistical evaluation using analysis of variance for repeated measures. The results of the study showed a net oxidative stress due to a single dialysis session in the form of increased plasma and erythrocyte lipid peroxidation, decrease in plasma vitamin E, slight increase in plasma superoxide dismutase and erythrocyte glutathione peroxidase and no change in plasma glutathione peroxidase. erythrocyte superoxide dismutase and plasma vitamin A levels. The oxygen radical production was found to be maximum in the first hour of dialysis.

Oxidative stress in haemodialysis: immediate changes caused by passage of blood through the dialyser.

Oxygen free radicals have been implicated in the long-term complications of maintenance haemodialysis. Studies that have probed into the mechanisms of oxygen radical production have implicated the bio-incompatibility of dialysis membranes. Changes between the arterial (inlet) and venous (outlet) points of a dialyser may give a better picture of blood membrane interaction. There are very few studies on changes across the dialyser. Hence, it was planned to study the immediate changes that occur due to passage of blood through the dialyser. Changes between the arterial and venous ends of the dialyser after 1 h of dialysis were studied in four combinations of dialysate and membrane. There was a significant decrease in plasma vitamin E concentrations in all the groups during first-use dialysis. This was not observed with re-use dialysis. A decrease in plasma lipid peroxides was also observed in all the groups with both first and re-use dialysis. There was no significant difference in the parameters studied among the four types of dialysis. A less severe, reactive oxygen radical generation was observed with re-use of membranes.

Intragastric long-term pH-metry in hemodialysis patients. A study with famotidine.

The onset and duration of famotidine action were studied in 14 hemodialysis (HD) patients and 16 healthy controls (control group: CG) who were examined by ambulatory intragastric 24-hour pH-metry. 20 mg famotidine was administered i.v. 90 min after HD in the afternoon (AN; 2 p.m.; n = 8) or evening (E; 8 p.m.; n = 6), followed by a standard meal. Mean onset of action in the AN and E groups of the HD patients was 90.3 +/- 28.2 min and 98.8 +/- 29.8 min, and in CG patients 36.3 +/- 11.9 min and 53.6 +/- 22.3 min, respectively (p less than 0.05). Duration of action in the AN and E groups of the HD patients was 22.7 +/- 2.1 h and 21.6 +/- 2.6 h, and in CG patients 6.0 +/- 1.1 h and 11.4 +/- 1.6 h, respectively (p less than 0.05). Our study showed a retarded and prolonged action of famotidine in HD patients. The time of administration of famotidine had no effect on its action in HD patients. This is in contrast to normal subjects in whom evening administration delays the onset and prolongs the duration of famotidine action in comparison to afternoon administration.

Secondary hyperparathyroidism and sonographic evaluation of parathyroid gland hyperplasia in dialysis patients.

Ninety-six hemodialysis patients were examined by ultrasonography of the parathyroid glands to study the prevalence of parathyroid gland hyperplasia and to assess the relevance of sonography in the evaluation of secondary hyperparathyroidism. The results were compared with clinical, biochemical and radiological parameters. Thirty-two (33.3%) patients had sonographically enlarged glands. Of them 19 had 1 and 13 had 2 and more enlarged glands. Patients with enlarged glands, compared to those with undetected glands, had a significantly higher frequency of bone and joint pains (65.5% vs 40.6%), radiological features of hyperparathyroid bone disease (in hands 28.1% vs 6.9%, in acromioclavicular joints 37.5% vs 13.6%) and higher levels of intact serum parathyroid hormone (1-84) concentration (52.8 +/- 47.9 pmol/l vs 18.1 +/- 18.0 pmol/l) and serum alkaline phosphatase concentration (260.2 +/- 201.1 U/l vs 129.8 +/- 127.3 U/l). Those with enlarged glands had been on dialysis for a longer period (87.7 +/- 51.0 months vs 62.5 +/- 47.4 months). The severity of secondary hyperparathyroidism increased with the number of enlarged glands. Our study shows that ultrasonography is a useful noninvasive screening method for the evaluation of secondary hyperparathyroidism in patients on hemodialysis and that sonographically enlarged glands may be a measure of the severity of secondary hyperparathyroidism.

Oxidative stress in hemodialysis--postdialytic changes.

BACKGROUND: There is evidence for production of free oxygen radicals during hemodialysis. Hemodialysis is an intervention that is intermittent and is usually undertaken once in two or three days. It is known that the free oxygen radicals are short lived. Hence, it is necessary to know how long the effects of this oxidative stress are seen in the postdialytic period and whether they are carried over to the next dialysis. Review of the literature showed that there is no information in this area. Hence, this study was undertaken in order to learn whether oxidative stress due to a dialysis session is carried over to next dialysis session or not. METHODS: The effects were studied after four different types of membrane and dialysate--Polysulphone-Bicarbonate (PB), Polysulphone-Acetate (PA), Cuprophan-Acetate (CA) and Cuprophan-Bicarbonate (CB). Two consecutive dialysis sessions were studied to know the effect of re-use of the membrane. For each dialysis session, blood samples were collected at 0 (immediately prior to dialysis or preHD), 4 (immediate postdialysis), 6, 12, 24 and 48 hours (start of next session). Lipid peroxides, SOD and GP were determined in erythrocytes. Vitamins A and E and lipid peroxides were estimated in plasma. RESULTS: In the postdialytic phase there was an increase in plasma lipid peroxide levels. Plasma vitamin E levels increased significantly in all groups after first use dialysis, whereas the increase found after re-use dialysis was not statistically significant. Erythrocyte lipid peroxide levels showed a significant decrease. No significant changes were observed in the plasma vitamin A, erythrocyte SOD and GP levels. There was no significant change in any of the parameters between preHD and either 48-hour or 96-hour samples in all groups studied. CONCLUSIONS: Our results show that there is no carry-over of oxidative stress produced by dialysis to the next session regardless of the type of dialysis.

Emphysematous renal tract disease due to Aspergillus fumigatus.

Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of renal parenchyma and/or urinary tract caused by gas producing organisms. A case of acute emphysematous renal tract disease (ERTD) (emphysematous pyelonephritis along with emphysematous cystitis) caused by Aspergillus fumigatus in a non-diabetic patient, who did not apparently have any risk factor for fungal infection, is presented. Patient had refused for any surgical intervention. He was treated successfully with liposomal amphotericin B and 5-flucytosin and achieved complete recovery. Various causes of ERTD and available therapeutic options are discussed.

Interferences in clinical chemistry analysis.

Analyses of body fluids in clinical chemistry laboratory are subject to a number of interferences that affect the analytical accuracy. The interferents arise from exogenous sources like drugs and additives as well as such endogenous sources like lipemia, hemolysis and icteria. Our studies demonstrate matrix interference in the form of analytical blas between serum and aqueous matrix calibrators. The clinical chemist should constantly be aware of this factor. Correction of interferences is recommended as an integral part of the quality assurance program.

Thyroid hormone profile in peritransplant period in live donor kidney transplantation.

Chronic renal failure, characterised by two factors acting in opposite directions with respect to the serum thyroid homone levels was chosen for the study. Healthy controls, donors undergoing nephrectomy and renal transplant recipients were studied. In transplant recipients, presurgical levels of total thyroxine(TT4), free triiodothyronine(FT3) and free thyroxine(FT4) were lower than controls, and immediately after the release of arterial clamps, there was an upsurge of total triiodothyronine (TT3), TT4, FT3 and FT4 due to administered and/or endogeneously secreted catecholamines. The levels of the 7th day were comparable to the presurgical levels. The changes observed in donors and recipients were similar indicating that the hormonal changes observed are mostly due to surgical stress. Recovery in the hormonal status did not start in the first week of posttransplant period.

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.

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.

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.

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.

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.

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.