Association Between Parathyroid Hormone-Related Peptide Levels and Mortality in Patients With Malignancy.

OBJECTIVE: Hypercalcemia of malignancy is a risk factor for mortality in patients with malignancies. Although the parathyroid hormone-related protein (PTHrP) secreted by tumor cells induces hypercalcemia, the association between serum PTHrP levels and mortality remains unclear. This study aimed to investigate the association between serum PTHrP levels and mortality in patients with malignancies. METHODS: We included patients with hypercalcemia (>10 mg/dL) and elevated PTHrP levels (>1.1 pmol/L) and analyzed mortality (overall survival after cancer diagnosis, PTHrP measurement, and 5-year survival rate). Moreover, using Cox proportional hazard model analysis, we investigated the impact of PTHrP levels on survival prognosis, assessing whether this effect varied depending on calcium concentration. RESULTS: We analyzed the data of 183 patients. The median PTHrP level, corrected calcium level, and age were 5.5 (3.0-10.6) pmol/L, 12.5 (11.5-13.4) mg/dl, and 70 (61-76) years, respectively. PTHrP was significantly and linearly associated with serum calcium levels (correlation coefficient, 0.06; 95% CI: 0.039-0.081, t: 5.69; P < .001). The group with the highest PTHrP levels had significantly worse survival rates than the group with the lowest PTHrP levels (hazard ratio: 1.68, 95% CI 1.03-2.77, P = .038). CONCLUSION: This study showed an association between PTHrP and mortality in patients with malignancy after adjusting for serum calcium levels.

Early Recurrence of Immunoglobulin A Nephropathy after Kidney Transplantation in a Patient with Down Syndrome.

A 39-year-old male kidney transplant recipient with Down syndrome (DS) was admitted to our hospital for biopsy. He had proteinuria at age 9, was diagnosed with immunoglobulin A nephropathy (IgAN) at age 22, had a tonsillectomy at age 35, and underwent ABO-compatible kidney transplantation (from his mother) at age 36. His serum creatinine was stable at 2.21 mg/dL 3 months after the kidney transplant, and his urine protein was 0.11 g/day. A protocol biopsy was performed 7 months after the kidney transplant, and there was suspicion of early recurrence of IgAN. One year after the transplant, urine erythrocytes were elevated and proteinuria was 0.41 g/day; at 3 years and 5 months after the kidney transplant, hematuria was evident along with proteinuria (0.74 g/day). Therefore, an episode biopsy was performed. A total of 23 glomeruli were obtained, four of which exhibited global sclerosis; three others showed intra- and extracapillary proliferative glomerulonephritis compatible with IgAN recurrence. Here, we report a rare case of early recurrence of IgAN with disease progression despite tonsillectomy in a patient with DS.

A case of pulmonary hyalinizing granuloma characterized by pseudohyponatremia due to hyperproteinemia.

A 57-year-old man presented with multiple pulmonary nodules. Thoracoscopic lung biopsy led to a pathological diagnosis of pulmonary hyalinizing granuloma (PHG) at the age of 39 years. The disease was progressive, refractory to therapy, and necessitated home oxygen therapy 10 years after the diagnosis. Hyponatremia progressed gradually along with lung disease. His serum sodium level was 129 mEq/L but serum osmolality was normal (287 mOsm/kg). Concomitant hyperproteinemia (12.1 g/dL) was attributable to hyperglobulinemia. Direct ion-selective electrode measurement revealed a normal sodium level (137 mmol/L). We herein report a case of PHG characterized by pseudohyponatremia due to hyperproteinemia, an uncommon finding in this rare entity. A left lung transplant was successfully performed, and no pseudohyponatremia was observed. Pseudohyponatremia should be suspected and diagnosed to prevent a misdiagnosis that could lead to complications from inappropriate treatment with sodium supplementation or restriction of drinking water. The direct ion-selective electrode measurement was useful for diagnosing pseudohyponatremia.

Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review.

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.

Interstitial fibroblasts in donor kidneys predict late posttransplant anemia.

BACKGROUND: Posttransplant anemia (PTA) is associated with the progression of kidney disease and mortality in kidney transplant recipients. Although the main causes of PTA are recipient factors, donor factors have not been fully investigated. In this study we investigated the association of donor pathological findings with the incidence of PTA in kidney transplant recipients after 3 years of transplantation. METHODS: We conducted a retrospective cohort study at a single university hospital. A total of 50 consecutive adult recipients and donors were enrolled. To assess the structure of interstitial lesions, immunohistochemical staining of interstitial fibrosis and fibroblasts were assessed in 0-h biopsies for quantitative analysis. RESULTS: The incidence of PTA in this cohort was 30%. The mean hemoglobin (Hb) was 11.6 ± 0.8 g/dL in patients with PTA and 14.3 ± 1.5 g/dL in patients without PTA. An inverse association was observed in biopsies between interstitial fibrosis area and interstitial fibroblast area (P < 0.01) and each pathological finding was examined for its association with PTA incidence after multivariate adjustment. For the interstitial fibrosis area, the odds ratio (OR) was 1.94 [95% confidence interval (CI) 1.26-2.99; P < 0.01]. For the interstitial fibroblast area, the OR was 0.01 (95% CI 0.00-0.16; P < 0.01). Receiver operating characteristics curve analysis indicated that the interstitial fibroblast area had high predictive power for the incidence of PTA. CONCLUSIONS: The presence of interstitial fibroblasts in donor kidneys may play an important role in predicting the incidence of PTA.

Hypercalcemia caused by comorbid parathyroid adenoma and pulmonary tuberculosis.

Hypercalcemia is usually secondary to one etiology, although two coexisting etiologies can rarely cause hypercalcemia. Here, we report a 47-year-old woman with hypercalcemia caused by comorbid parathyroid adenoma and pulmonary tuberculosis. Primary hyperparathyroidism is the most common cause of hypercalcemia. Tuberculosis is a rare cause of hypercalcemia, but Japan continues to have an intermediate tuberculosis burden. Therefore, tuberculosis should be considered as a cause of hypercalcemia in Japan. Patients with tuberculosis are often asymptomatic, making the diagnosis difficult. In the previous cases in which these diseases coexisted, one disease was diagnosed after treatment of the other. In our case, the very high 1,25-dihydroxyvitamin D level (162 pg/mL) helped us to diagnose asymptomatic tuberculosis and both diseases were diagnosed promptly. It is necessary to consider comorbidities, including tuberculosis in a case with a very high 1,25-dihydroxyvitamin D level. We report a valuable case in which the early diagnosis and treatment of tuberculosis and primary hyperparathyroidism prevented the spread of tuberculosis.

Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation.

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.

Dysfunctional ABCG2 gene polymorphisms are associated with serum uric acid levels and all-cause mortality in hemodialysis patients.

Dysfunctional variants of ATP-binding cassette transporter subfamily G member 2 (ABCG2), a urate transporter in the kidney and intestine, are the major causes of hyperuricemia and gout. A recent study found that ABCG2 is a major transporter of uremic toxins; however, few studies have investigated the relationship between ABCG2 gene polymorphisms and mortality. This prospective cohort study of 1214 hemodialysis patients investigated the association between serum uric acid levels and ABCG2 genotype and mortality. Genotyping of dysfunctional ABCG2 variants, Q126X (rs72552713) and Q141K (rs2231142), was performed using the patients' DNA. During the study period, 220 patients died. Lower serum uric acid levels were associated with higher mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.14-3.10, P ≤ 0.001). ABCG2 dysfunction, estimated by genetic variants, had a significant positive association with serum uric acid levels (full function: 7.4 ± 1.2 mg/dl, 3/4 function: 7.9 ± 1.3 mg/dl, 1/2 function: 8.2 ± 1.4 mg/dl, ≤ 1/4 function: 8.7 ± 1.3 mg/dl, P ≤ 0.001). This association remained significant on multiple regression analysis. The Cox proportional hazard analysis indicated that the ABCG2 ≤ 1/4 function type was significantly associated with higher mortality (HR 6.66, 95% CI 2.49 to 17.8, P ≤ 0.001) than the other function types. These results showed that ABCG2 plays a physiologically important role in uric acid excretion, and that ABCG2 dysfunction is a risk factor for mortality in hemodialysis patients.

Association between resistin and fibroblast growth factor 23 in patients with type 2 diabetes mellitus.

Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease and all-cause mortality in patients with diabetes mellitus. Insulin resistance has recently been reported to increase FGF23 levels, and resistin is a peptide that mainly regulates insulin resistance. However, few studies have investigated the association between FGF23 and resistin. A total of 422 patients with diabetes mellitus were recruited for this cross-sectional study to examine the association between resistin and intact FGF23. The mean ( ± standard deviation) age was 63.1 ± 11.9 years, and the median HbA1c was 6.7% (range, 6.1-7.1%). The mean estimated glomerular filtration rate (eGFR) was 66.2 ± 23.1 mL/min/m2. Multiple regression analysis for resistin showed that logFGF23 (coefficient (Coef): 1.551; standard error (SE): 0.739; P = 0.036), C-peptide (Coef: 0.798; SE: 0.229; P = 0.001), ghrelin (Coef: 1.061; SE: 0.332; P = 0.001), intact parathyroid hormone (Coef: 0.022; SE: 0.099; P = 0.030), and eGFR (Coef: -0.091; SE: 0.017; P < 0.001) were all significantly associated with the resistin level. These associations were modified in patients with higher age, lower body mass index, and higher vitamin D levels. These results suggest that resistin is positively associated with serum FGF23 levels.

Antibody-mediated rejection due to anti-HLA-DQ antibody after pregnancy and delivery in a female kidney transplant recipient.

Herein, we report a case of antibody-mediated rejection (ABMR) due to anti-HLA-DQ antibody after pregnancy and delivery in a female kidney transplant recipient. A 34-year-old female recipient was admitted at 2 years after delivery for an examination of an elevated serum creatinine (S-Cr) level. The patient had received a living kidney transplantation from her mother at 22 years of age, and her kidney graft function was almost stable. The episode biopsy showed peritubular capillaritis and transplant capillaropathy with C4d immunoreactivity in the peritubular capillaries. Additional examination revealed expression of a donor-specific antibody (DSA) against HLA-DQ5, leading to the diagnosis of chronic active ABMR. Intravenous immunoglobulin, plasma exchange, and rituximab were administered, and her S-Cr level was maintained stable. This case demonstrates a possible relationship between pregnancy/delivery and development of ABMR due to a de novo DSA in a female kidney transplant recipient.

Successful treatment of recurrent immunoglobulin a nephropathy using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation: a case presentation.

BACKGROUND: Both prevention and treatment of recurrent immunoglobulin A nephropathy (IgAN) in kidney transplant recipients are important since recurrent IgAN seems to affect long-term graft survival. We present here a case of recurrent IgAN that was successfully treated using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation. CASE PRESENTATION: A 46-year-old male was admitted for an episode biopsy with a serum creatinine level of 1.8 mg/dl and proteinuria (0.7 g/day). Histological features showed recurrent IgAN (only focal segmental mesangial proliferation) and severe arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity, with limited interstitial fibrosis and tubular atrophy (5%) (IF/TA) 8 years after transplantation. Sodium restriction and conversion from cyclosporine to tacrolimus successfully reduced his proteinuria to the level of 0.15 g/day. However, 2 years later, his proteinuria increased again (1.0 g/day) and a second episode biopsy showed global mesangial proliferation with glomerular endocapillary and extracapillary proliferation accompanied by progressive IF/TA (20%). The steroid pulse therapy plus tonsillectomy successfully decreased his proteinuria and he achieved clinical remission 3 years after this treatment. CONCLUSION: This case, presented with a review of relevant literature, demonstrates the difficulty and importance of the treatment of recurrent IgAN and calcineurin inhibitor arteriolopathy, especially in long-term kidney allograft management.

Association Between GLCCI1 Promoter Polymorphism (Rs37972) and Post-Transplant Hypertension in Renal Transplant Recipients.

BACKGROUND/AIMS: Post-transplant hypertension is highly prevalent in renal transplant recipients and is a risk factor for graft loss, cardiovascular disease and death. Glucocorticoid is used to prevent rejection, but simultaneously increases the risk of post-transplant hypertension. The glucocorticoid-induced transcript 1 (GLCCI1) promoter polymorphism (rs37972) has been reported to be associated with response to glucocorticoid therapy in asthma. We therefore examined the association between GLCCI1 promoter polymorphism and post-transplant hypertension in renal transplant recipients. METHODS: We conducted a retrospective cohort study of renal transplantation at a single university hospital from October 2003 to January 2014. Fifty consecutive adult recipients were analyzed, with clinical data retrieved from a prospectively collected database. Genotyping was carried out using genomic DNA derived from recipient's blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively analyzed by immunohistochemical staining of recipients' native kidney biopsy-specimens. The primary outcome measure was post-transplant hypertension. RESULTS: Post-transplant hypertension was observed in 14/17 (82%) of recipients with CC, 18/20 (90%) with CT, and 2/13 (15%) with TT genotype. CC/CT genotype was significantly associated with post-transplant hypertension, even after adjustment for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P = 0.026). In addition, we observed that GLCCI1 immunoreactivity in arteriolar endothelial cells was higher in kidney specimens obtained from recipients with a CC/CT genotype than a TT genotype (P = 0.021). CONCLUSION: GLCCI1 promoter polymorphism rs37972 may be associated with post-transplant hypertension.

Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease.

Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced serum inorganic phosphorus (Pi) as compared to that in the control. The histopathology of the kidneys showed a greater dilation of tubular lumens and interstitial fibrosis in the control group. Calcium and Pi contents of the aorta in the ASCs transplantation group were lower than those in the control group. Von Kossa staining of the thoracic aorta media revealed that ASCs transplantation suppressed vascular calcification. Thus, this study revealed that autogenic ASCs transplantation inhibits kidney damage and suppresses the progression of vascular calcification in the CKD rat model, suggesting that autogenic ASCs transplantation is a novel approach for preventing the progression of CKD and vascular calcification.

Successful Treatment of Plasma Cell-Rich Acute Rejection Using Pulse Steroid Therapy Alone: A Case Report.

Despite the recent development of immunosuppressive agents, plasma cell-rich acute rejection (PCAR) has remained refractory to treatment. Herein, we report an unusual case of PCAR that responded well to pulse steroid therapy alone. A 47-year-old man was admitted for a protocol biopsy three months after kidney transplantation, with a stable serum creatinine level of 1.6 mg/dL. Histological examination showed focal aggressive tubulointerstitial inflammatory cell infiltration of predominantly polyclonal mature plasma cells, leading to our diagnosis of PCAR. Three months following three consecutive days of high-dose methylprednisolone (mPSL) therapy, an allograft biopsy performed for therapy evaluation showed persistent PCAR. We readministered mPSL therapy and successfully resolved the PCAR. Although PCAR generally develops more than six months after transplantation, we diagnosed this case early, at three months after transplantation, with focally infiltrated PCAR. This case demonstrates the importance of early diagnosis and prompt treatment of PCAR to manage the development and severity of allograft rejection.

The prognostic values of caveolin-1 immunoreactivity in peritubular capillaries in patients with kidney transplantation.

The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection (CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts (ENDATs). We previously showed that the ENDAT caveolin-1 (CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients. Ninety-eight kidney transplant recipients were included in this study. The prognostic value of CAV-1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV-1 and pathologische Anatomie Leiden endothelium (PAL-E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV-1/PAL-E<50% and CAV-1/PAL-E≥50%. Kaplan-Meier curves showed that CAV-1/PAL-E≥50% patients had a significantly worse prognosis than that of CAV-1/PAL-E<50% patients (log-rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log-rank; P=.345), whereas in a multivariate Cox regression analysis, CAV-1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV-1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.

Successful treatment of recurrent Henoch-Schönlein purpura nephritis in a renal allograft with tonsillectomy and steroid pulse therapy.

We report a case of recurrent Henoch-Schönlein purpura nephritis (HSPN) treated successfully with a tonsillectomy and steroid pulse therapy in a kidney transplant patient. A 29-year-old woman was admitted to our hospital for an episode biopsy; she had a serum creatinine (S-Cr) of 1.0 mg/dL and 1.34 g/day proteinuria 26 months after kidney transplantation. Histological examination revealed increased amounts of mesangial matrix and mesangial hypercellularity with IgA deposition. Of note, one glomerulus showed focal endocapillary proliferation and tuft necrosis. We diagnosed active recurrent HSPN. Considering both the histological findings and refractory clinical course of the native kidney, she was treated for 3 consecutive days with steroid pulse therapy and a tonsillectomy. The patient's proteinuria decreased gradually to less than 150 mg/day 6 months later. A second biopsy 6 years after kidney transplantation showed an excellent response to treatment and revealed a marked reduction in both the mesangial matrix and mesangial hypercellularity, with trace IgA deposition. We conclude that a tonsillectomy and steroid pulse therapy appeared to be useful in this patient with active recurrent HSPN. This paper is the first to report a tonsillectomy and steroid pulse therapy as a therapeutic option for active recurrent HSPN. Further studies are needed to elucidate the efficacy and mechanisms of tonsillectomy with recurrent HSPN in kidney transplant patients.

Subclinical antibody-mediated rejection due to anti-human-leukocyte-antigen-DR53 antibody accompanied by plasma cell-rich acute rejection in a patient with cadaveric kidney transplantation.

A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti- human-leucocyte-antigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to human-leucocyte-antigen-DR53 and plasma cell-rich acute rejection.

Rare case of nephrocalcinosis in the distal tubules caused by hereditary renal hypouricaemia 3 months after kidney transplantation.

We report a rare case of nephrocalcinosis caused by hereditary renal hypouricaemia 3 months after kidney transplantation. A 41-year-old man who underwent living-related kidney transplantation from his father was admitted to our hospital for a protocol biopsy; he had a serum creatinine (S-Cr) of 1.37 mg/dL and no proteinuria. Histologically, there was no evidence of rejection or calcineurin inhibitor toxicity, although scattered nephrocalcinosis was observed in the distal tubules. Perioperatively, the patient had a serum uric acid (S-UA) of 1.9 mg/dL with a fractional excretion of uric acid (FEUA) of 29% (normal, <10%) and UA clearance of 26.8 mL/min (normal, 7.3-14.7 mL/min) 3 days after kidney transplantation. The donor also had a relatively low S-UA of 2.4 mg/dL and high FEUA of 10.3%. Subsequent DNA direct sequencing followed by restriction fragment length polymorphism revealed that both the recipient's and donor's urate transporter 1 (URAT1) gene had a heterozygous nonsense mutation in exon 5 (C889T). Further, the immunoreactivity of antibodies for the C terminus of URAT1 revealed a partial deletion. De Galantha and von Kossa staining revealed that the nephrocalcinosis was due to urate crystals and calcium stones. Therefore, we diagnosed hereditary renal hypouricaemia. We directed the patient to avoid hard exercise, drink plenty of water, and alkalize the urine. The 1-year follow-up allograft biopsy showed no evidence of nephrocalcinosis in the distal tubules. This is the first report of nephrocalcinosis in the distal tubules as a diagnostic clue to hereditary renal hypouricaemia. We also review the related literature.

Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange.

Myeloma cast nephropathy is a major complication of multiple myeloma. Recent evidence has demonstrated that the earlier induction of bortezomib-based chemotherapy with plasma exchange (PE) provides better results for kidney function and patient survival. Due to its non-selectivity, PE with albumin replacement carries the risk of fibrinogen loss, leading to bleeding. We herein report a case of successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20-year history of type II diabetes mellitus was admitted to our hospital for the evaluation of hypercalcemia, severe kidney dysfunction, and anemia. Subsequent bone marrow evaluation and renal biopsy revealed that she had multiple myeloma (IgG-κ) and myeloma cast nephropathy. Ten days after admission, bortezomib-based chemotherapy with selective PE achieved rapid and thorough free light-chain (FLC) reduction; within a month, her kidney function had been recovered (creatinine level, 1.2 mg/dl). Her serum fibrinogen level was not reduced, and no bleeding complication occurred. Five months later, autologous hematopoietic stem-cell transplantation was performed successfully, and the patient's kidney function was stable (creatinine level, 1.1 mg/dl) thereafter. This case report demonstrates the importance of early induction therapy with bortezomib-based chemotherapy and PE in a patient with myeloma cast nephropathy, which is especially applicable in patients aged <65 years. In addition, it shows that selective PE is a safe and effective method of FLC removal.

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.