Change in glomerular volume and its clinicopathological impact after kidney transplantation.

BACKGROUND: Both immunological and non-immunological etiologies affect graft function after kidney transplantation, including acute rejection, calcineurin inhibitor toxicity, and a recurrence of glomerulonephritis. Glomerular enlargement or glomerular sclerosis due to glomerular hyperfiltration related to increased renal blood flow is another cause. Although the glomerular volume in baseline biopsies predicts late allograft function, the relationship between allograft function and the annual changes in glomerular volume after kidney transplantation are unclear. AIM: We investigated changes in glomerular volume after kidney transplantation and their clinicopathological relationship. METHODS: We enrolled 23 patients with stable kidney function without an episode of rejection or any complication resulting in a functional decrease in the graft. We measured glomerular volume (GV) using the Weibel-Gomez method and glomerular density (GD) using 0,1 h biopsy samples as baseline controls and 1 yr biopsy samples and investigated the association between the changes in them and clinical parameters, including graft function, proteinuria, and renal hemodynamic markers, including effective renal plasma flow (ERPF) and filtration fraction (FF). The ERPF was calculated from a 99mTc-mercaptoacetyltriglycine (MAG3) renogram. RESULTS: The GV and ERPF increased significantly 1 yr after kidney transplantation. In contrast, proteinuria decreased significantly and Δproteinuria (1 yr - 1 month after transplantation) was correlated with ΔGV (P < 0.05, rs = -0.467). CONCLUSION: Glomerular enlargement 1 yr after transplantation may be related to improved proteinuria. It is possible that glomerular enlargement serves as a renal adaptation after kidney transplantation.

Monitoring of body water composition by the simultaneous use of bioelectrical impedance analysis and Crit-Line(®) during hemodialysis.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a non-invasive method to estimate total body water (TBW) and extracellular water (ECW) volume. Crit-Line(®) (CL), on the other hand, assesses intravascular water (IVW) volume. We evaluate continuous changes in body water composition during hemodialysis (HD) with concurrent use of BIA and CL. METHODS: BIA at the start and the end of the HD session was measured using a BIA device. To investigate the shifting pattern of body water composition, patients were subjected to simultaneous monitoring of BIA with CL. RESULTS: Both TBW resistance (Rt) and ECW resistance (Re) increased in response to changes in the ultrafiltration (UF) ratio. There was a positive correlation between ΔRe/Rt and the UF ratio, and the ratio of Re/Rt at the end of HD was significantly higher than that at the start of HD. Simultaneous monitoring of BIA with CL showed a parallel shift of the change in the Re (ΔRe) and the change in hematocrit (ΔHt). In one patient with increasing inflammatory response, change in ΔHt was dissociated from change in ΔRe. One hyponatremic patient showed a different pattern of changing ΔRe between the first half and the latter half of the HD session. CONCLUSION: Our study suggests that the concurrent use of BIA and CL may be a useful technique to simulate water shift patterns across the different compartments in HD.

Increased lymphatic vessels in patients with encapsulating peritoneal sclerosis.

BACKGROUND: The angiogenic response is partly involved in the progression of encapsulating peritoneal sclerosis (EPS). However, the details of the angiogenic response, especially for lymphatic vessels in patients with EPS, remain unclear. In addition, because of technical limitations, morphology studies reported to date have examined only the parietal peritoneum. The morphologies of parietal and visceral lymphatic vessels in patients with EPS both need to be analyzed. METHODS: We examined peritoneal samples from 18 patients with EPS who underwent enterolysis of the visceral peritoneum and compared them with samples from 17 autopsy cases (controls). To examine the angiogenic response, we performed immunohistochemistry for the endothelial markers CD34 (blood vessels) and podoplanin (lymphatic vessels) and for the cell proliferation marker Ki-67. Immunogold electron microscopy analysis for podoplanin was also performed. In 7 of 18 cases, we compared differences in the angiogenic response of the parietal and visceral peritoneal membranes. RESULTS: Angiogenic responses were more frequent in the compact zone than in regenerated layers. The number of capillaries positive for anti-CD34 and anti-podoplanin monoclonal antibodies per unit area of visceral peritoneal tissue was, respectively, 41.1 ± 29.3/mm(2) in EPS patients and 2.7 ± 4.4/mm(2) in controls (p ≤ 0.01) and 48.1 ± 43.9/mm(2) in EPS patients and 4.1 ± 5.4/mm(2) in controls (p ≤ 0.01). The percentage of capillaries positive for anti-Ki-67, CD34, and podoplanin was 4.6% in EPS patients (p ≤ 0.01) and 0.8% in controls (p = 0.09). The immunogold electron microscopy analysis revealed that podoplanin was localized to endothelial cells with anchoring filaments, a specific feature of lymphatic vessels. Furthermore, compared with parietal peritoneal membrane, visceral peritoneal membrane had a more prominent podoplanin-positive capillary profile, but not a prominent CD34-positive capillary profile. In addition, fibroblast-like cells double-positive for podoplanin and smooth muscle actin were markedly increased in the degenerated layer, as previously reported. CONCLUSIONS: Our study demonstrated that lymphatic vessels are increased in the visceral peritoneum of patients with EPS.

Morning hypertension determined by self-measurement at home predicts left ventricular hypertrophy in patients undergoing continuous ambulatory peritoneal dialysis.

This study aimed to clarify the relationship between blood pressure (BP, mm Hg) measured by patients in the morning at home and left ventricular hypertrophy (LVH), which is a strong predictor for morbidity and mortality due to cardiovascular disease in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We recorded self-measured morning BPs and BPs measured at hospital check-ups (hospital BPs) in 33 patients undergoing CAPD (mean age, 64.0 years) and compared them with left ventricular mass (LVM) derived from echocardiographic examinations. The mean morning BP was 137/75, the mean hospital BP was 140/80, and the mean LVM (g/m(2.7) : corrected by height) was 61.8. Of the subjects, 72.7% had LVH (LVM > 51). The morning BP (systolic) was positively correlated with LVM (P = 0.0022, R = 0.508), and the hospital BP (systolic) was weakly correlated (P = 0.0534, R = 0.339). The adjusted odds ratio for LVH was significantly higher in patients with a morning BP (systolic) ≥ 135 (15.9; 95% CI, 1.3 to 198.5) than in patients with a morning BP (systolic) < 135. In conclusion, morning hypertension determined with self-measured BP was positively correlated with LVH, therefore self BP monitoring could be a useful method to predict LVH in CAPD patients.

A lower level of reduced albumin induces serious cardiovascular incidence among peritoneal dialysis patients.

BACKGROUND: Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and of oxidized human non-mercaptoalbumin. Previously, we reported that a lower HMA level is closely related to serious cardiovascular disease (CVD) incidence and mortality among hemodialysis patients. However, the relationship between HMA level and CVD incidence among peritoneal dialysis (PD) patients is unclear. METHODS: We measured the redox state of human serum albumin using high-performance liquid chromatography in 30 continuous ambulatory PD patients. The association between HMA and incidental CVD events was evaluated. RESULTS: Eight patients experienced symptomatic CVD events (5 patients died) at the 5-year follow-up. The concentration and fraction of HMA (cHMA and f(HMA), respectively) showed significantly lower values in patients with CVD than those without CVD (cHMA 1.58 ± 0.39 and 2.16 ± 0.43 g/dL, f(HMA) 48.9 ± 5.4 and 56.4 ± 8.6%, respectively). Multiple forward stepwise regression analysis using cHMA and f(HMA) as the criterion variables was performed, and C-reactive protein and hemoglobin were adopted as significant explanatory variables in the former equation, whereas urea nitrogen was adopted in the latter equation. Multiple logistic regression analysis revealed that cHMA is a statistically, and f(HMA) is a marginally significant explanatory variable of CVD incidence (p = 0.0369, R = -0.260 and p = 0.0580, R = -0.214, respectively). CONCLUSIONS: Lower HMA level, which might be caused by chronic inflammation, anemia and accumulation of dialyzable uremic toxin(s), is closely related to serious CVD incidence among PD patients.

Successful treatment of nephrotic syndrome caused by recurrent IgA nephropathy with chronic active antibody-mediated rejection three years after kidney transplantation.

Here, we report the successful treatment of a 38-yr-old Japanese man diagnosed with recurrent immunoglobulin A nephropathy (IgAN) with chronic active antibody-mediated rejection (CAAMR), three yr after undergoing living-related donor kidney transplantation. Immediately after transplantation, the allograft function was well maintained with a serum creatinine (S-Cr) level of <1.8 mg/dL. About three yr after transplantation, urine protein excretion had reached 4.59 g/d, and the S-Cr level had increased to more than 2.0 mg/dL. Based on the allograft biopsy, we diagnosed nephrotic syndrome because of recurrence of IgAN with CAAMR. Subsequently, we performed a tonsillectomy, administered three sessions of steroid pulse therapy, and added losartan for the recurrence of IgAN. We also changed his immunosuppressant from mizoribine to mycophenolate mofetil to treat the CAAMR. The nephrotic syndrome improved with the multiple therapeutic approaches; however, the S-Cr level did not decrease below 2.0 mg/dL. We possibly could have performed additional treatments such as rituximab and intravenous immunoglobulin for the CAAMR, but therapeutic strategies for CAAMR have not yet been established.

Nonenzymatic cross-linking pentosidine increase in bone collagen and are associated with disorders of bone mineralization in dialysis patients.

Disorders of bone and mineral metabolism are common complications in chronic kidney disease (CKD) patients and lead to significantly increased fracture risk, morbidity, and mortality of cardiovascular disease due to ectopic calcifications, contributing to a worsening prognosis. Bone strength is determined by not only bone mineral density but also bone quality, which is dependent on bone collagen cross-links. Collagen cross-links are classified into enzymatic immature and mature types and nonenzymatic advanced glycation end products (AGEs). Pentosidine is well established as one of the AGEs that accumulates markedly in CKD patients. The chemistry, function, and clinical relevance of cross-links have been revealed, whereas bone quality and the relationship with bone mineralization in CKD patients are not clear. We performed transiliac bone biopsies on 22 dialysis patients (mean age 56 ± 9 years) with severe secondary hyperparathyroidism and measured cross-links by evaluating bone histomorphometry. Cross-links data were compared with age-matched non-CKD subjects (mean age 58 ± 8 years, n = 17). Enzymatic collagen cross-links were formed to a similar extent compared with non-CKD subjects and showed a positive correlation with plasma intact parathyroid hormone. Pentosidine was remarkably increased in dialysis patients and inversely correlated with bone-formation rate/bone volume and mineral apposition rate. This study suggests that AGE collagen cross-links strongly associate with disorders of bone metabolism in dialysis patients.

Successful treatment of recurrent focal segmental glomerulosclerosis combined with calcineurin inhibitor nephrotoxicity four yr after kidney transplantation.

A 31-yr-old Japanese man with end-stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent living related kidney transplantation at the age of 26 yr. The allograft functioned well immediately after surgery, and we did not observe histological findings of rejection and recurrent FSGS in protocol biopsies at two months and one yr after transplantation. Four years after transplantation, the urine protein excretion reached 11 g/d, and the serum creatinine increased over 2.5 mg/dL. We diagnosed nephrotic syndrome due to recurrent FSGS with graft dysfunction and confirmed FSGS lesions with severe endothelial injury with an allograft biopsy, associated with calcineurin inhibitor (CNI) nephrotoxicity. Thereafter, we performed plasmapheresis and steroid therapy with subsequent low-density lipoprotein adsorption, combined with the reduction of tacrolimus. The nephrotic syndrome improved dramatically with the multiple therapeutic approaches. Primary FSGS recurs frequently in patients immediately after kidney transplantation. Post-transplant FSGS has various causes, such as recurrent primary disease, obesity, hyperfiltration, donor-related nephrosclerosis, and CNI-induced arteriolopathy. In the case of nephrotic syndrome after kidney transplantation, we should consider not only recurrent FSGS, but also CNI-induced nephrotoxicity to determine the optimal treatment.

A case of accelerated acute rejection after ABO-compatible living unrelated kidney transplantation.

A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.

Secondary focal segmental glomerulosclerosis following kidney transplantation in a patient with type I diabetes mellitus.

Although recurrent diabetic nephropathy is common in patients with type I diabetes after kidney transplantation, the development of focal segmental glomerulosclerosis (FGS) is rare, and its development generally takes several years. We report here a case of type I diabetes mellitus with secondary FGS accompanied by proteinuria 10 months following kidney transplantation. Episode biopsy showed secondary FGS, evidenced by glomerular capillary collapse and large epithelial cells with ballooning degeneration. Exudative dense deposition of IgM in a diffuse global mesangial pattern and enlarged glomerular diameters were observed, suggestive of glomerular hyperfiltration which can lead to secondary FGS. An imbalance in body size between donor and recipient and/or uncontrolled diabetes are potential causes of glomerular hyperfiltration. We administered angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker to reduce hyperfiltration-induced renal damage; the combination therapy reduced proteinuria from 2346 to 258 mg/d. Secondary FGS should be a consideration after kidney transplantation in patients with type I diabetes mellitus.

[Dialysis as bridge therapy for renal transplantation: single center experience, a comparison of hemodialysis and continuous ambulatory peritoneal dialysis].

BACKGROUND: Kidney transplantation is the most ideal treatment in renal replacement therapy for patients with end-stage renal disease. However, the prevalence of transplantation is extremely low and most patients with ESRD should continue dialysis for their whole life. Recently, high transposition rate of renal transplantation from peritoneal dialysis (PD) was reported, however, it was unclear whether a difference in dialytic modality can influence the outcome. Therefore, we evaluated the influence of dialytic modality on the rate of kidney transplantation and outcome in our single center. METHODS: Forty-two kidney transplants were carried among 1,573 dialysis patients from the years 1986 to 2004 in our center. Transposition rates from two modalities (HD and PD) and graft survival were compared. The incidence of acute rejection episode, complications after receiving transplantations, and coexisting diseases were also evaluated between the two modalities prior to transplantation. RESULT: The number of patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively). Forty-two patients undergoing dialytic therapy received a living-donor kidney transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years. Among these cases, dialytic modality prior to transplantation was 57.1% in HD, and 42.9% in PD. The transfer rate from PD to transplantation was significantly (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high transfer rate of PD patients might be cooperation with their family and the provision of relevant information by nephrologists during PD. There were no differences between the two modalities prior to transplantation in the graft survival rate, incidence of acute rejection, and complications before and after transplantation. CONCLUSION: Difference in pretransplant dialysis modality did not affect the outcomes, however, the transfer rate from PD was significantly higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy for kidney transplantation from the high feasibility of living-donor kidney transplantation.

A case of renal sarcoidosis: a special reference to calcium metabolism as a diagnostic and the therapeutic implications.

Sarcoidosis is a systemic granulomatous disease of unknown etiology and is associated with a wide variety of renal disorders including nephrolithiasis, hypercalciuria, hypercalcemia, nephrocalcinosis, tubular defect, glomerulonephritis, and granulomatous interstitial nephritis. We report a case of renal sarcoidosis in which we could not detect any evidence of extrarenal involvements that was diagnosed by renal biopsy and abnormal calcium metabolism incompatible with chronic renal insufficiency. On laboratory findings, decreased creatinine clearance, proteinuria, hypercalcemia, hypercalciuria, and mildly elevated serum angiotensin-converting enzyme (ACE) were seen. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,alpha-25 vit D) were lower and higher than normal range, respectively, whereas the patient was already in chronic renal insufficiency. He was treated with oral corticosteroid. Serum ACE tended to fall, and 1,alpha-25 vit D level decreased with substantial fall of serum calcium and daily calcium excretion. In contrast, intact PTH increased slowly in accordance with a fall of serum calcium compatible with the level of renal impairment. Creatinine clearance and daily excretion of protein improved. The case reported here may propose that serial measurement of serum level of 1,alpha-25 vit D, calcium level, and magnitude of daily calcium excretion into urine is a simple and meaningful tool to detect the therapeutic response in sarcoidosis with abnormal calcium metabolism.