The role of uric acid in chronic kidney disease patients.

AIM: Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients. METHODS: A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor. RESULTS: The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P < 0.001), and an HR of 1.12 for cardiovascular disease (CVD) hospitalization (P = 0.02), but not significantly with all-cause mortality and cardiovascular death at the end of follow-up. CONCLUSIONS: In stage 3-5 CKD patients, hyperuricaemia was associated with a higher risk of renal replacement therapy, rapid renal progression and hospitalization for all causes or CVD, but not with all-cause mortality or cardiovascular mortality.

U-shaped relationship between uric acid and residual renal function decline in continuous ambulatory peritoneal dialysis patients.

AIM: There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. METHODS: A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. RESULTS: The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (<0.372 mmol/L), higher UA group (≧0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria. CONCLUSIONS: A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups.

Empyema associated with peritoneal dialysis peritonitis.

A 65-year-old woman on peritoneal dialysis (PD) was admitted due to abdominal pain with cloudy PD effluent. The white blood cell count in PD effluent was 5860/µL with 85% polymorphonuclear neutrophils. Therefore, she was clinically diagnosed with peritonitis. The cultures of PD effluent were negative. Initial abdominal computed tomography did not find suggest any intraabdominal pathology. The patient was treated with empirical intraperitoneal antibiotics. Because abdominal pain with cloudy PD effluent persisted, the PD catheter was removed eventually. The culture of the removed PD catheter grew Klebsiella pneumoniae. However, intermittent fever was noted over the following days and empyema developed approximately 2 weeks after PD catheter removal. The culture of pleural fluid also grew K. pneumoniae. Another computed tomography revealed multiple intraabdominal abscesses that was assumed to come from a complication of PD-associated peritonitis. We postulate that the empyema might be caused by transdiaphragmatic extension of the intraabdominal abscesses into the pleural space.

Necrotizing fasciitis caused by Serratia marcescens: a fatal complication of nephrotic syndrome.

Necrotizing fasciitis is an uncommon complication of nephrotic syndrome. There have been only four cases of necrotizing fasciitis complicating nephrotic syndrome reported in the English literature. We report a 40-year-old woman with minimal-change nephrotic syndrome receiving cyclosporine therapy, who suffered from necrotizing fasciitis of her left leg. Cultures of blood and surgical specimens yielded Serratia marcescens. Despite aggressive treatment, the patient expired shortly after surgery. We review the literature and find eight cases of necrotizing fasciitis caused by S. marcescens. Most of these patients had an immunocompromised background, and the mortality rate was high.

An unusual case of Gitelman's syndrome with hypercalcemia.

We reported a case of a 41-year-old woman who had been diagnosed with Gitelman's syndrome since the age of 31 years. The diagnosis was established by the typical biochemical pictures including renal wasting hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. She had normal blood pressure and had never used diuretics. She had a sibling with similar syndrome. The patient was treated with oral potassium and magnesium supplementation. She began to have hypercalcemia at the age of 39 years. The diagnostic approach to hypercalcemia became more complicated because of normal parathyroid hormone levels and underlying hypocalciuria due to Gitelman's syndrome. Thorough evaluation eventually identified primary hyperparathyroidism as the cause of hypercalcemia. To our best knowledge, this is the first report of combined occurrence of Gitelman's syndrome and primary hyperparathyroidism in the literature.

IgA variant of anti-glomerular basement membrane glomerulonephritis associated with pulmonary hemorrhage and microangiopathic hemolytic anemia.

A 70-year-old man with uremia was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgA along the glomerular basement membrane (GBM). No thrombotic microangiopathy was noted on renal biopsy. Circulating IgG anti-GBM antibody was not detected, and IgA anti-GBM antibody was not tested. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.

Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

Favorable outcome of crescentic IgA nephropathy associated with methicillin-resistant Staphylococcus aureus infection.

Dominant or codominant IgA deposits in the setting of proliferative glomerulonephritis usually indicate IgA nephropathy, Henoch-Schönlein purpura nephritis, or, sometimes, lupus nephritis. However, a new type of poststaphylococcal glomerulonephritis with predominantly IgA deposition has been increasingly reported. Herein, we report an unusual case of rapidly progressive glomerulonephritis following methicillin-resistant Staphylococcus aureus infection. Renal biopsy showed crescentic IgA nephropathy. The renal function improved after eradication of infection and administration of immunosuppressive therapy. Although the limited data support the use of immunosuppressive agents in this setting, one must proceed with caution. We suggest that immunosuppressive therapy should only be an option if the underlying infection has definitely been well controlled while the renal disease still progresses.

IgA-dominant postinfectious glomerulonephritis: not peculiar to staphylococcal infection and diabetic patients.

BACKGROUND: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. METHODS: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. RESULTS: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1 mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p = 0.007). There were no significant differences in other clinical parameters and outcome between the two groups. CONCLUSIONS: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.

Sustained low-efficiency daily diafiltration with hemoperfusion as a therapy for severe star fruit intoxication: a report of two cases.

Over the past decade, star fruit (Averrhoa carambola) intoxication decreased in the Taiwanese society due to improved public education on chronic kidney disease (CKD). Various complications including hiccups, altered levels of consciousness, coma, and seizures have been reported in individuals with renal failure who ingested fresh star fruit or star fruit juice. A high mortality rate (from 33 to 80%) was observed in patients with altered levels of consciousness, despite prompt dialysis and supportive care. According to previous case reports, the proposed treatment of choice for severe star fruit intoxication may be continuous renal replacement therapy with or without hemoperfusion. We report two cases of star fruit intoxication with stage V CKD (one case is predialysis) presenting with coma and generalized tonic-clonic seizures. The two patients were treated with sustained low-efficiency daily diafiltration (SLEDD-f) and charcoal hemoperfusion. Status epilepticus was controlled fairly quickly after treatment with SLEDD-f and hemoperfusion. However, the outcomes in this report are still poor (both remained comatose; one of two patients died). Currently, there are no data for the use of SLEDD-f with hemoperfusion for severe star fruit intoxication. SLEDD-f with charcoal hemoperfusion may play a role in managing refractory status epilepticus in patients with severe star fruit poisoning.

The spectrum of acute renal failure in IgA nephropathy.

BACKGROUND: Acute renal failure rarely complicates the course of IgA nephropathy. In this study, we have tried to define the mode of presentation, the spectrum of morphology, and the prognostic factors for renal outcome. METHODS: Twenty patients with biopsy-proven IgA nephropathy who developed acute renal failure were identified from 2000 to 2009 at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, morphology of renal biopsy, and outcomes. RESULTS: On histology, glomerular crescents were present in 11 patients (55%), acute tubular necrosis was identified in 11 patients (55%), acute interstitial nephritis was seen in 4 patients (20%), and extensive tubular red blood cell casts were present in 4 patients (20%). At the end of follow-up, 2 patients (10%) had died, 11 patients (55%) were in remission, and 7 patients (35%) developed end-stage renal disease. The prognostic factors for renal outcome were peak serum creatinine, dialysis support requirement, morphology (prominent glomerular/tubular injury), percentage of glomeruli affected by crescents, and interstitial infiltration (p = 0.04, <0.001, 0.013, 0.05, 0.02, respectively). CONCLUSIONS: Our findings suggested that there were four pathogenic mechanisms involved in IgA nephropathy with acute renal failure including (1) crescentic IgA nephropathy; (2) acute tubular necrosis associated with microhematuria and red blood cell casts occluding tubules; (3) acute tubular necrosis not related to microhematuria; and (4) acute interstitial nephritis, apparently induced by drugs. In general, patients with prominent tubular injury had a much higher remission rate than patients with prominent glomerular injury.

Discrimination between postinfectious IgA-dominant glomerulonephritis and idiopathic IgA nephropathy.

BACKGROUND: A unique form of postinfectious glomerulonephritis (PIGN) with IgA-dominant deposition mimicking IgA nephropathy has been increasingly reported. METHODS: We compared the clinical and histological features of 12 patients with postinfectious IgA-dominant glomerulonephritis to 134 patients with idiopathic IgA nephropathy. RESULTS: In addition to hypocomplementemia and subepithelial hump-shaped deposits characteristic of PIGN, patients with postinfectious IgA-dominant glomerulonephritis had older age (62.3 +/- 16.9 vs. 37.9 +/- 16.3 years; p < 0.001) and more frequently presented with acute renal failure (83.3% vs. 10.4%; p < 0.001) than patients with idiopathic IgA nephropathy. Moreover, glomerular changes including endocapillary proliferation, neutrophil infiltration, and capillary loops deposits by immunofluorescence were more commonly present in postinfectious IgA-dominant glomerulonephritis group (p < 0.001). CONCLUSIONS: PIGN could be characterized by glomerular IgA-dominant deposition resembling idiopathic IgA nephropathy. It is essential to differentiate postinfectious IgA-dominant glomerulonephritis from idiopathic IgA nephropathy because of the different treatments and prognosis of the two diseases.

Clinicopathological study of originally non-lupus "full-house" nephropathy.

BACKGROUND: Glomerular "full-house" immunofluorescence staining commonly indicates lupus nephritis. However, some non-lupus nephropathy also can present with a "full-house" immunofluorescence pattern mimicking lupus nephritis. The goal of this study is to define the clinicopathological spectrum of originally non-lupus "full-house" nephropathy. METHODS: Records of 24 patients with "full-house" nephropathy in the absence of clinical or serological evidence of systemic lupus erythematosus (SLE) at the time of renal biopsy were abstracted for demographics, clinical presentation, laboratory data, renal biopsy findings, and clinical follow-up. RESULTS: The clinicopathological diagnoses included membranous glomerulonephritis (GN) (46%), IgA nephropathy (21%), membranoproliferative GN (12.5%), postinfectious GN (12.5%), C1q nephropathy (4%), and unclassified mesangial GN (4%). No one had endothelial tubuloreticular inclusions. One patient originally diagnosed as IgA nephropathy developed anti-DNA antibody and another one patient with membranous GN developed hypocomplementemia 8 months and 10 months after renal biopsy, respectively. The two patients also developed clinical symptoms of lupus subsequently. CONCLUSIONS: There was a broad spectrum of glomerular histological findings in non-lupus "full-house" nephropathy. The possibility of "full-house" nephropathy preceding the emergence of overt systemic lupus erythematosus remained to be elucidated.

Differences in new-onset IgA nephropathy between young adults and the elderly.

BACKGROUND: The goal of this study was to define the clinical and histological differences in new-onset IgA nephropathy between young adults and the elderly. METHODS: We retrospectively examined renal biopsy findings, clinical features at presentation and outcomes in 82 young adults (mean age 30.3+/-10.2 years) and 17 elderly patients (mean age 71.9+/-4.5 years) with IgA nephropathy whose renal biopsies were taken within 1 year from the onset of renal manifestations. RESULTS: The elderly group more frequently had hypertension (p<0.001), acute renal failure (p<0.001), and nephrotic range proteinuria (p=0.001) at presentation than the young adults group. On histology, a higher percentage of globally sclerotic glomeruli (p<0.001) was present in the elderly group. In patients presenting with acute renal failure, the elderly group more frequently had an intercurrent disease (p=0.02), mostly infection, and a higher mortality rate (p=0.033). On histology, the young adults group had a higher percentage of glomeruli affected by crescents (p=0.027); in contrast, the elderly group more commonly had acute tubular injury (p=0.02). CONCLUSIONS: The elderly patients affected by IgA nephropathy had more severe renal manifestations at presentation (acute renal failure in 52.9% and nephrotic syndrome in 41.2% of patients). In cases of acute renal failure, the elderly patients had more predominant tubular rather than glomerular injury. Moreover, the considerable mortality rate (44.4%) might be associated with the intercurrent disease, mostly infection, which was more commonly present in the elderly patients.

Comparison of typical endocapillary and atypical mesangial proliferation in postinfectious glomerulonephritis.

BACKGROUND: There is a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis (PIGN). We conducted this retrospective study to compare the clinicopathological features between two distinct morphology of PIGN. METHODS: Thirteen patients with typical endocapillary proliferation and eight patients with atypical mesangial proliferation were enrolled in this study. The patients' records were reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. RESULTS: In comparison of histological parameters, glomerular neutrophil infiltration was more commonly present in typical endocapillary proliferation group (p = 0.018). Glomerular IgA dominant or co-dominant deposition was more frequently seen in atypical mesangial proliferation group (p = 0.032). In a comparison of clinical parameters, atypical mesangial proliferation group had lesser degrees of proteinuria, higher serum levels of complement, and higher rates of staphylococcal infection, although none of the differences was statistically significant. Glomerular morphology did not seem to affect the renal outcome. Moreover, our data suggested that the percentage of patients with atypical mesangial proliferation significantly increased over time (p < 0.001). CONCLUSIONS: Atypical mesangial proliferation may represent a resolution stage of PIGN. The nature of subclinical infection with a more protracted course may contribute to the increasing recognition of this resolving PIGN at the time of renal biopsy. Another possible explanation is that the atypical morphology may be a peculiar pattern of post-staphylococcal glomerulonephritis, which was increasingly identified in PIGN over the past 10 years.