Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. METHODS: Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. RESULTS: Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6-53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. CONCLUSIONS: Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

Comparison of the pain-reducing effects of EMLA cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: A multi-center, open-label, randomized crossover trial.

Arteriovenous fistula puncture pain is a serious problem for patients undergoing dialysis and a good indication for topical anesthetics. No previous study has compared lidocaine/prilocaine cream (EMLA) with lidocaine tape for pain relief during arteriovenous fistula puncture in patients undergoing maintenance hemodialysis. To this end, we conducted a multicenter randomized crossover study including 66 patients (mean age, 65.8 years; males, 57.6%) undergoing maintenance hemodialysis thrice/week. Subjects were assigned to Sequence EL (EMLA administration followed by lidocaine, with 1-week wash-out) or Sequence LE (reverse administration, first lidocaine then EMLA). All subjects completed the study. At each puncture site, 1 g EMLA (25 mg lidocaine + 25 mg prilocaine) or one sheet of lidocaine tape (18 mg lidocaine) was applied 1 h or 30 min prior to arteriovenous fistula puncture, respectively. The primary endpoint was puncture pain relief, which was measured using a 100-mm visual analog scale. The secondary endpoints included quality of life, which was measured by SF-36, and safety. EMLA produced a 10.1-mm greater visual analog scale improvement than lidocaine tape (P = 0.00001). However, there was no statistically significant difference in the quality of life between the two groups, and no significant carryover/period effect was observed in any analysis. Further, no drug-related adverse events were observed. Taken together, these results suggest that EMLA cream is superior to lidocaine tape for the relief of arteriovenous fistula puncture pain in patients undergoing maintenance hemodialysis. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000027885).

Clinical significance of serum and urinary soluble urokinase receptor (suPAR) in primary nephrotic syndrome and MPO-ANCA-associated glomerulonephritis in Japanese.

BACKGROUND: The soluble urokinase receptor (suPAR) has been implicated as a cause of primary focal segmental glomerulosclerosis (FSGS). However, the clinical significance of suPAR in glomerular diseases currently remains unclear. METHODS: In this retrospective single-center cohort study, we investigated serum (s-) and urinary (u-) suPAR in patients with primary nephrotic syndrome (NS) (serum/urine: 37/32 cases) and MPO-ANCA-associated glomerulonephritis (ANCA-GN) (serum/urine: 13/11 cases). RESULTS: In pretreatment s- and u-suPAR, no significant differences were observed between the primary NS and ANCA-GN groups or among the pathological types of primary NS. An inverse correlation was noted between pretreatment s-suPAR and eGFR in the primary NS and ANCA-GN groups. A positive correlation was noted between pretreatment u-suPAR and proteinuria in the primary NS group. Furthermore, time-course changes in s- and u-suPAR over 2 months after therapy were associated with the therapeutic responsiveness of primary NS, particularly the differentiation of MCNS from FSGS (s-suPAR: AUC-ROC = 0.905, p = 0.007; u-suPAR: AUC-ROC = 0.816, p = 0.048). In the ANCA-GN group, a positive correlation was found between pretreatment s-suPAR and clinical severity or crescent formation, whereas u-suPAR was not correlated with these parameters. CONCLUSION: S- and u-suPAR after therapy may serve as clinical markers to judge the treatment response of untreated NS and differentiate MCNS from FSGS, but not in pretreatment patients. S-, but not u-suPAR may predict the severity of and crescent formation in ANCA-GN.

Successful delivery in a patient with antineutrophil cytoplasmic antibody-associated glomerulonephritis.

We herein report a case of spontaneous pregnancy and preterm delivery in a 29-year-old patient with myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Her basal serum creatinine level before pregnancy was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The proteinuria and hematuria increased during pregnancy, and the patient was admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of gestation, she delivered a live infant weighing 848 g via cesarean section. No relapse of ANCA-associated glomerulonephritis occurred.

Circulating fibrocytes in ischemia-reperfusion injury and chronic renal allograft fibrosis.

BACKGROUND: Interstitial fibrosis in chronic allograft injury has been suggested as a major cause of the loss of allograft. METHODS: To clarify the involvement of circulating fibrocytes (CF) and α-smooth muscle actin (SMA)-positive cells in renal allograft injury, we investigated 36 renal transplanted cases at 0 h, 1 h, 2-4 weeks, 4-8 weeks, and 1 year, and 5 normal controls. Double immunofluorescence analysis for both COL1 and CD45 indicating CF (/mm(2)), and the positive area (%) of α-SMA and Masson trichrome (MT) stain were detected by an image analyzing system. RESULTS: The mean number of CF was 0 in controls and 4.0 in total transplanted specimens (p < 0.05). CF correlated with the α-SMA-positive area in the graft (R(2) = 0.39, p < 0.01), but not with Banff 2005 scores. The number of CF increased in 2-4 weeks; however, decreased 1 year after transplantation. α-SMA-positive area gradually increased at 1 year concomitant with the increase of MT-positive area. A similar phenomenon was observed in a case of primary nonfunction kidney from 0 h to 6 weeks after transplantation. The electron microscopy score of fibrosis around peritubular capillaries was correlated positively with COL1-positive area (R(2) = 0.72, p < 0.01), but negatively with infiltrated CF (R(2) = 0.25, p < 0.05). CONCLUSION: CF were transiently induced, probably due to ischemia-reperfusion injury, but fibrosis only slightly progressed in this process. The α-SMA-positive myofibroblasts may accelerate the expansion of fibrosis around peritubular capillaries in chronic allograft injury.

A case of chronic hepatitis C with nephrotic diabetic nephropathy who achieved sustained viral remission by double-filtration plasmapheresis and interferon combination therapy.

We report a 66-year-old man with chronic hepatitis caused by hepatitis type C virus of genotype-1b and high-viral-load combined with cryoglobulinemia and advanced diabetic nephropathy in whom we successfully achieved viral removal and eradication by DFPP (VRAD). The dose of PEG-interferon was reduced to 70 mg/week due to thrombocytopenia. Rivavirin was discontinued at day 21 due to anemia. Even with treatment of PEG-interferon alone, the condition was judged to be sustained viral remission at the end of the observation. This is a successful report of VRAD in a combined case of diabetic and HCV-related cryoglobulin-nephropathy with nephrotic syndrome. The therapeutic effect of IFN seemed to be efficiently enhanced by concomitant DFPP (VRAD therapy).

A case of second renal transplantation with acute antibody-mediated rejection complicated with BK virus nephropathy.

We reported a 40-year-old female case of second renal transplantation with antibody-mediated rejection (AMR) complicated by BK virus nephropathy. She started hemodialysis (HD) at the age of 17 because of IgA nephropathy. At the age of 18, she underwent living-donor kidney transplantation from her father, but two and a half years after transplantation, she developed chronic rejection. This time, she received cadaveric renal transplantation under the negative cross-match (AHG-LCT), and HLA-AB 1 mismatch and -DR 1 mismatch. Immunosuppressive therapy was initiated using the following four immunosuppressants: methylprednisolone, mycophenolate mofetil, cyclosporine, and basiliximab. However, renal graft showed delayed function, the biopsy showed glomerulitis (g2), endarteritis (v1), and cellular infiltration (ptc3) consisting mainly of mononuclear cells in the peritubular capillary with diffusely positive C4d and anti-SV 40 large T-antigen-positive renal tubular epithelial cells on post-operative day 19. The donor-specific antibody for HLA-B46 was proven by the LAB screen method. We performed plasma exchange three times and administered immunoglobulin (15 g in total). Then, methylprednisolone pulse therapy was added, and the serum creatinine (SCr) levels gradually decreased. On post-operative day 44, the patient was removed from HD and was discharged with SCr level of 3.3 mg/dL.

[Relationship between initial diagnosis and long-term prognosis in lupus nephritis].

UNLABELLED: To clarify the outcomes of patients with lupus glomerulonephritis (LGN), we performed a retrospective study of 31 patients (27 females and 4 males) with LGN between January 1975 and June 2006. All these 31 patients fulfilled the SLE criteria of the American College of Rheumatology evaluated by pathohistological diagnosis using renal biopsies. According to 2003 ISN/RPS classification, we reclassified all initial renal biopsies as class II 16%, class III 16%, class IV 48%, and class V 19.5%. Activity and chronicity indices were also calculated according to the scores proposed by Austin et al. All patients were treated by oral corticosteroids in induction therapy, then subsequeatly 18 patients (61%) were treated with intravenous methylprednisolone pulse therapy, and 16 patients with immunosuppressive agents (58%). Clinical remission rate was 94% by induction therapy and 13% by recurrence rate. Patient survival rate was 85% at 10 years and 76% at 20 years. Renal survival rate was 96% at 10 years and 86% at 20 years, 100% at 10 years and 80% at 20 years in ClassIV-G. In the multivariate Cox hazard analysis of the clinicopathologic factors, serum creatinine was selected as the most significant risk factor for death and/or end-stage renal failure (p=0.036). In addition, the chronicity index was also a significant risk factor for renal survival of LGN. CONCLUSION: This retrospective analysis of LGN showed better outcomes than expected. Overall, early diagnosis and suitable initial therapy may improve the renal survival of LGN in both groups of patients.