Chishio Munemura

Epidermal Growth Factor and Endothelin in Cyst Fluid From Autosomal Dominant Polycystic Kidney Disease Cases: Possible Evidence of Heterogeneity in Cystogenesis

We determined the concentrations of immunoreactive epidermal growth factor (EGF), endothelin (ET), and cyclic adenosine monophosphate (cAMP) in cyst fluid from 10 nondialyzed patients with autosomal dominant polycystic kidney disease (ADPKD). The concentrations of ET and cAMP in low-sodium cyst fluid (cyst sodium concentration < 100 mEq/L) were significantly increased compared with those in high-sodium cyst fluid (cyst sodium concentration > or = 100 mEq/L), but the concentration of EGF did not differ between the two. There was no relationship between cyst fluid volume and EGF, ET, cAMP values in ADPKD cases. Significant variations of cyst fluid concentrations of EGF, ET, and cAMP were observed among the patients. However, the differences of these variables between the right and left kidney of the individual subjects were unremarkable. Serum levels of creatinine and urea nitrogen showed significant negative correlations with EGF, but not with ET and cAMP. The present data demonstrate the differences in cytokine activity among cysts in ADPKD cases, suggesting the heterogeneity of cystogenesis along the tubular segments in this particular disease.

Cyst sclerotherapy with minocycline hydrochloride in patients with autosomal dominant polycystic kidney disease

BACKGROUND The enlarged cysts in autosomal dominant polycystic kidney disease (ADPKD) frequently cause abdominal discomfort. Cyst sclerotherapy with minocycline hydrochloride was performed to relieve this symptom. METHODS Ten symptomatic ADPKD cases were recruited. As a sclerosant, minocycline hydrochloride solution (10 mg/dl) was used. This solution was instilled into the cysts under ultrasonographic control. Renal volume was calculated before therapy and at 6-month intervals thereafter. Renal function and blood pressure were regularly monitored. The effect of sclerotherapy on symptoms was also assessed at 6-month intervals. RESULTS At 6 months, renal volume was statistically lower than the presclerotherapy, and was associated with improvement in chronic symptoms. However, such ameliorating effects were blunted at 12 months. Renal volume reduction at 6 and 12 months showed a significant positive correlation with the dose of minocycline injected. No significant influence in renal function and blood pressure was observed. CONCLUSIONS These results suggest that cyst sclerotherapy with minocycline hydrochloride is a valid treatment regime for the relief of chronic symptoms in ADPKD cases, although repeated application of this approach may be required to obtain a more long-term effect.

Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment.

Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors.

Long-Term Effects of Enalapril in Rat with Experimental Chronic Tubulo-interstitial Nephropathy

The aim of this study was to determine whether or not angiotensin-converting enzyme inhibitor, enalapril, could ameliorate the chronic tubulo-interstitial nephropathy (TIN) in uninephrectomized (UNx) rats. Chronic TIN(M) was induced by 2-bromoethylamine hydrobromide. Rats were assigned to five groups; control, UNx-control (UNxC), UNx treated with enalapril (UNxE), UNxMC and UNxME. Enalapril was given for 12 months as drinking water (50 mg/l). At 6 months, albuminuria in UNxE decreased significantly compared with UNxC, but without change in UNxM rats. By 12 months, although all rats in control, UNxC and UNxE remained alive, 1 and 4 rats died in UNxME and UNxMC, respectively. Albuminuria in UNxC was reduced significantly by enalapril but not in UNxM rats. Both urine volume and urine osmolality became equal to control by enalapril in UNx rats, but not in UNxM rats. Serum cholesterol levels were normalized by enalapril in UNx rats, but not in UNxM rats. Levels of serum creatinine and blood urea nitrogen were invariably higher in UNxM than in UNx rats, irrespective of enalapril. Glomerular sclerosis was statistically decreased by enalapril in both UNx and UNxM rats. Enalapril reduced the overall tubulo-interstitial lesions in UNx rats, but not in UNxM group. However, in UNxM rats tubular changes in medullary portion were significantly ameliorated by enalapril. These data suggest that enalapril has a beneficial effect on chronic TIN in this model.

Apoptosis induced by an uromodulin mutant C112Y and its suppression by topiroxostat

BackgroundFamilial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder caused by mutations in UMOD that encodes uromodulin. Topiroxostat, a novel non-purine analog, selectively inhibits xanthine oxidase and reduces the serum uric acid levels and the urinary albuminuria.MethodsGenomic DNA of a patient was extracted from peripheral white blood. Exons and flanking sequences of UMOD were amplified by PCR with primers. Mutation analysis was performed by direct sequencing of the PCR products. The wild-type and mutant uromodulin were expressed in HEK293 cells and analyzed by western blotting, immunoprecipitation, immunofluorescence, and flow cytometry.ResultsWe identified an FJHN patient who carried a novel UMOD mutation G335A (C112Y). The levels of both cytosolic and secreted C112Y protein were significantly decreased compared with the wild-type, whereas the level of ubiquitination was higher in C112Y than that in the wild type. The half-life of C112Y was shortened and it was restored by a proteasome inhibitor MG132. Immunofluorescence revealed decreased levels of C112Y in the Golgi apparatus and on the plasma membrane. Expression of C112Y induced cellular apoptosis as revealed by flow cytometry. Apoptosis induced by C112Y was suppressed by topiroxostat.ConclusionC112Y causes its protein instability resulting cellular apoptosis which could be suppressed with topiroxostat.

Shewanella algae Bacteremia in an End-stage Renal Disease Patient: A Case Report and Review of the Literature

A 71-year-old man was admitted because of nausea and abdominal pain. He was receiving an erythropoiesis-stimulating agent for anemia and dysregulated iron metabolism due to stage G5 chronic kidney disease. He had a history of raw fish intake and was diagnosed with infectious enterocolitis, which worsened and led to septic shock. Shewanella putrefaciens grew in the blood culture, but Shewanella algae was identified in a 16S rRNA gene sequence analysis. We herein report a case of S. algae bacteremia believed to have been transmitted orally. We also reviewed previous case reports on Shewanella infection in end-stage renal disease patients.

Biochemical characteristics of cyst fluid in undialysed patients with autosomal dominant poiycystic kidney disease

Summary: The biochemical composition of cyst fluid was analysed in 148 cysts obtained from 10 patients with autosomal dominant polycystic kidney disease (ADPKD). Serum creatinine levels ranged from 1.7 to 9.0 mg/dL. No patients were receiving renal replacement therapy. Aspirated cyst volume ranged from 4‐120 mL. There was no significant correlation between cyst volume and cyst sodium concentration ([Na]cyst). Cyst sodium concentration demonstrated a bimodal distribution pattern, with one peak from 10‐20 mEq/L and the other from 140‐150 mEq/L. the ratios of cyst fluid versus serum sodium concen tration ([Na]cyst/serum) were positively correlated with [C1]cyst/serum, while negatively correlated with [K]cyst/serum, [Ca]cyst/serum, [P]cyst/serum and [UA]cyst/serum. Based on the [Nalcyst/serum, the cysts were assigned to three types: proximal (0.8‐1.4), indeterminant (0.4–0.8) and distal (<0.4). the percentage of each type was 54.7, 19.6 and 25.7%, respectively. There were no significant differences in [Na]cyst/serum between the right and left kidney in individual patients. the concentrations of amino acids were higher in the distal type than in the proximal type.

Tubulointerstitial Nephritis with IgM-Positive Plasma Cells

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3--Cl- anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell-tubulointerstitial nephritis.

Left Renal Cortical Thickness Measured by Ultrasound Can Predict Early Progression of Chronic Kidney Disease

Aims: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. Methods: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥90; group 2, ≥60 but <90; group 3, ≥30 but <60; and group 4, <30. Renal US parameters in both kidneys were compared among the 4 groups. Results: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. Conclusion: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.