Tenascin-C expression in renal biopsies from patients with tubulointerstitial nephritis and its relation to disease activity and prognosis.

Tenascin-C (TNC) is an extracellular matrix protein that is transiently expressed in close association with tissue remodeling in various organs. Expression of TNC in patients with tubulointerstitial nephritis (TIN) is not well-characterized. Using renal biopsy specimens from 25 patients with TIN and 8 patients with thin basement membrane disease (controls), we assessed immunohistochemical staining for TNC and investigated its relation with clinicopathologic data. TNC was undetectable in the controls, but TNC was observed in the interstitium of specimens from all patients with TIN, and strong TNC staining was detected within active tubulitis lesions. TNC was not principally expressed in glomeruli, and it was also absent from scar tissue. Comparison with Sirius red staining revealed that TNC was present where collagen fibers had not yet formed. The percent area of TNC within the interstitium (% TNC-positive area) showed a significant negative correlation with illness duration and significant positive correlations with the serum CRP level and eGFR aggravation, both of which reflect disease activity. On the other hand, no correlation was found between % TNC-positive area and eGFR recovery during 2 years of follow up. Examination of renal biopsy specimens from TIN patients revealed that TNC appears during the active stage of inflammation and then disappears with healing. This suggests that TNC expression reflects TIN disease activity, but not prognosis.

Correlation between renal function and common risk factors for chronic kidney disease in a healthy middle-aged population: a prospective observational 2-year study.

BACKGROUND/AIMS: Age, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor. METHODS: In total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses. RESULTS: Over 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR. CONCLUSION: The changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.

Expression of prorenin receptor in renal biopsies from patients with IgA nephropathy.

Prorenin receptor (PRR) has been implicated in the onset and progression of various renal diseases, though its possible association with immunoglobulin A (IgA) nephropathy remains unclear. In the present study, we tried to clarify expression and pathophysiological significance of PRR in IgA nephropathy. We immunohistochemically assessed PRR levels in renal biopsy specimens from 48 patients with IgA nephropathy and evaluated its relevance to the clinical and pathological features of the disease. PRR was detected mainly in renal tubular cells, which was confirmed at the subcellular level using immunoelectron microscopy. The PRR-positive area (%PRR area) correlated with daily urinary protein, which is known to reflect disease severity (r=0.286, P=0.049). PRR levels were weaker in tubular cells bordering areas of severe interstitial fibrosis, where α-smooth muscle actin-positive myofibroblasts were present. We also used immunohistochemical detection of microtubule-associated protein-1 light chain 3 (LC3) and electron microscopy to assess autophagy, a cytoprotective mechanism downstream of PRR. We noted an apparent coincidence between autophagy activation in tubular cells and PRR expression in the same cells. Taken together, our findings suggest that renal expression of PRR in IgA nephropathy may be a compensatory response slowing disease progression by preventing tubular cell death and subsequent fibrosis through activation of cytoprotective autophagic machinery. Further studies using different type of kidney diseases could draw conclusion if the present finding is a generalized observation beyond IgA nephropathy.

Lanthanum carbonate for hyperphosphatemia in patients on peritoneal dialysis.

BACKGROUND: The efficacy of the phosphate binder lanthanum carbonate has been demonstrated for hemodialysis patients, but no studies have focused on patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We evaluated whether lanthanum carbonate could control phosphate levels in patients on CAPD. ♢ METHODS: In this 48-week open-label prospective study, 28 patients on CAPD with a phosphate level of 6 mg/dL or greater were given lanthanum carbonate titrated from 750 mg to 2250 mg daily to achieve a target serum phosphate level of less than 6 mg/dL. The primary efficacy endpoint was reduction of serum phosphate to less than 6 mg/dL. Serum levels of calcium and parathyroid hormone were also evaluated, as were the Ca×P product and adverse effects. ♢ RESULTS: From week 4 to the end of the study at week 48, we observed a significant reduction of serum phosphate to 5.25 ± 0.97 mg/dL from 6.88 ± 1.06 mg/dL at study start (p < 0.01). At the end of the study, 78.6% of participants had achieved the target of less than 6 mg/dL. Because no change of serum calcium occurred, the Ca×P product declined significantly during the study. Intact parathyroid hormone declined gradually over the study period, but the change had not reached significance at the end of the study (p = 0.11). The mean final dose of lanthanum carbonate was 946 mg daily. The only adverse effect reported was mild nausea in 1 patient. ♢ CONCLUSIONS: Lanthanum carbonate is an effective phosphate binder that can control serum phosphate and Ca×P product in CAPD patients with hyperphosphatemia. Lanthanum carbonate was well tolerated in our population.

[A case of urethrovesical foreign body in an adolescent boy].

We report an unusual case of a 14-year old boy who presented with proteinuria and pyuria detected in a medical checkup at school. After denial of kidney disease, computed tomography of the pelvis showed a bladder stone with an internal low density and urethroscopy showed an odd stick at the prostatic urethra. Because of the failure of removal by the transurethral technique, he underwent suprapubic cystostomy against the foreign body stuck into the prostatic urethra. After surgery, he admitted that he had self-introduced a sewing instrument into the bladder for the purpose of masturbation one year three months previously.

Tertiary hyperparathyroidism resistant to cinacalcet treatment.

Cinacalcet hydrochloride (cinacalcet) has been reported to be efficacious for patients with tertiary hyperparathyroidism (THPT). We experienced five patients with THPT requiring parathyroidectomy (PTx) because of resistance to cinacalcet treatment and investigated their clinical characteristics and clinical course. The maximum diameter of the parathyroid gland estimated by ultrasonography before renal transplantation was evaluated. Serum total calcium, phosphorus, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and creatinine (Cr) levels were investigated every three months after the administration of cinacalcet and at PTx. After surgery, the Cr levels were followed. In all five patients, at least one parathyroid gland had a largest diameter of more than 1 cm, and the mean diameter was 18.7 mm (range 14.9-24.1 mm). Intact PTH and ALP levels gradually increased after the initiation of cinacalcet and the Cr levels transiently increased after PTx. These findings suggest that the existence of a severely enlarged nodular hyperplastic gland is a main factor involved in resistance to cinacalcet.