Shinji Tomikawa

Infected hepatic and renal cysts: differential impact on outcome in autosomal dominant polycystic kidney disease.

Background: Infected cysts are a frequent and serious complication of autosomal dominant polycystic kidney disease. Such infections are classified into those affecting hepatic cysts and those affecting renal cysts. The purpose of this study was to compare the clinical course of infected hepatic cysts with that of infected renal cysts in patients with autosomal dominant polycystic kidney disease. Methods: We analyzed 43 patients referred to us for additional treatment of severely infected cysts between January 2004 and December 2006. All patients who required further treatment in addition to antibiotic therapy were included. Results: Aspiration was performed in all 28 patients with infected hepatic cysts. As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One patient was cured by partial hepatectomy. Among the 15 patients with renal cysts, aspiration was performed in 4 with identifiable infected cysts, while renal transcatheter arterial embolization after appropriate antibiotic therapy was performed in 11 without identifiable infected cysts. No patient developed recurrence. Conclusion: In patients with infected renal cysts, aspiration or renal transcatheter arterial embolization after appropriate antibiotic therapy was effective. Although aspiration was often effective in patients with infected hepatic cysts, a good outcome was less likely than in those with renal cysts.

Histopathological alterations of the parathyroid glands in haemodialysis patients with secondary hyperparathyroidism refractory to cinacalcet hydrochloride

Background Cinacalcet treatment for secondary hyperparathyroidism (SHPT) has demonstrated parathyroid size regression and morphological changes, such as cystic degeneration and hypovascularisation, on ultrasonography.; However, there have been very few reports regarding the histopathological alterations of hyperplastic parathyroid glands in patients with SHPT after administration of cinacalcet. The aim of this study was to elucidate the effects of cinacalcet for histopathological alterations on the parathyroid glands. Methods A total of 92 hyperplastic parathyroid glands were obtained from 24 dialysis patients with severe SHPT who underwent total parathyroidectomy and were enrolled in this study. Patients were divided into those treated with and without cinacalcet (cinacalcet group and conventional group, respectively; both n=12). The areas of oxyphil cells, cystic degeneration, haemorrhagic changes and haemosiderin deposition were assessed semiquantitatively. Results Total maximal parathyroid gland weight and maximal-to-minimal parathyroid gland weight ratio were significantly higher in the cinacalcet group compared with the conventional group (1798.7±1658.3 mg vs 764.2±471.1 mg, p=0.018, 15.8±13.9 vs p=0.047, 6.6±4.2, respectively). Significant increases were observed in oxyphil cell area (61.7%±17.1% vs 36.7%±15.6%, p=0.001) and haemosiderosis score (1.50±1.24 vs 0.42±0.51, p=0.029) in the former rather than the latter group. Conclusions These results suggest that cinacalcet may induce specific qualitative alterations of hyperplastic parathyroid glands in patients with severe SHPT.

Cinacalcet upregulates calcium-sensing receptors of parathyroid glands in hemodialysis patients.

Background: Cinacalcet hydrochloride (cinacalcet), a calcimimetic, has been shown to upregulate calcium-sensing receptor (CaSR) expression in parathyroid glands of rats with chronic renal insufficiency. However, the effect of cinacalcet on the reduced CaSR expression in human parathyroid glands remains to be elucidated. Methods: Four normal parathyroid glands and 71 hyperplastic parathyroid glands from 18 hemodialysis patients with refractory secondary hyperparathyroidism (SHPT) treated with (n = 10; cinacalcet group) or without (n = 8; conventional group) cinacalcet were examined immunohistochemically with a specific antibody against CaSR. The expression level of CaSR was analyzed semiquantitatively. Results: Compared with normal glands, the immunohistochemical expression of CaSR was decreased significantly in both the cinacalcet and conventional groups. In the cinacalcet group, the expression of CaSR was increased significantly compared with that in the conventional group (1.83 ± 0.14 vs. 0.87 ± 0.15, p < 0.001), even though the proportion of patients using vitamin D sterols and the mean administered dose of calcitriol equivalents were not significantly different between the two groups. The expression of CaSR was significantly decreased in the larger glands (>500 mg) compared with that in the smaller glands (<500 mg) in both groups; furthermore, it was markedly decreased in areas of nodular hyperplasia compared with diffuse hyperplasia in the cinacalcet group. Conclusions: Our results indicate that cinacalcet upregulates the depressed expression of CaSR in hemodialysis patients with SHPT, and that insufficient expression of CaSR, especially in larger glands with advanced nodular hyperplasia, underlies the pathogenesis of SHPT in patients who are resistant to cinacalcet.

Renal Cell Carcinoma in Autosomal Dominant Polycystic Kidney Disease

p g E utosomal dominant polycystic kidney disease (ADPKD) is one of the most common ereditary kidney disorders and accounts for 8% o 10% of patients with end-stage renal failure in he United States and Europe. In some patients ith ADPKD, the kidneys continue to enlarge fter the initiation of dialysis therapy, resulting in uch significant complications as cyst bleeding nd abdominal distention. Keith et al previusly reported that renal cell carcinoma (RCC) is serious complication of ADPKD, but the incience of RCC in patients with ADPKD is controersial because the total number of patients with nderlying ADPKD has not been clarified. In the present study, we discuss the role of maging studies and the incidence of RCC in a enter’s experience with dialysis patients with DPKD.

Recurrent Proliferative Glomerulonephritis With Monoclonal IgG Deposits of IgG2λ Subtype in a Transplanted Kidney: A Case Report

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a recently described disease entity. In the kidney transplantation literature, only 6 recurrent and 2 de novo PGNMID cases, including 7 of the IgG3 subclass (6 with κ light chain and 1 with λ light chain) and 1 of the IgG1 subclass (λ light chain), have been described to date. We describe a 52-year-old man with end-stage renal disease whose primary glomerular disease had been suggested to be membranoproliferative glomerulonephritis. The patient underwent living related donor kidney transplantation and presented with proteinuria, hematuria, and decreased kidney function at 4 months posttransplantation. Biopsy of the transplanted kidney showed diffuse endocapillary proliferative glomerulonephritis. Immunofluorescence microscopy showed prominent granular glomerular staining for IgG, C3, and λ light chain, with IgM, IgA, and κ light chain undetectable. Immunofluorescence staining for IgG subclass showed signal for IgG2 only. Retrospective analysis of the native kidney biopsy specimen also showed the same monoclonal glomerular staining for the IgG2λ subtype. These findings led us to the diagnosis of PGNMID of the IgG2λ subtype as both the primary glomerular disease and recurrent disease in the transplanted kidney. Recurrence was treated with high-dose prednisolone, which decreased proteinuria, hematuria, and serum creatinine level. The case demonstrates that PGNMID of the IgG2λ subtype also can recur in the transplanted kidney.

Effects of percutaneous ethanol injection therapy on subsequent surgical parathyroidectomy

Background. Renal hyperparathyroidism (RHPT) is a serious complication of long-term dialysis treatment. Two intervention methods can be administered to treat RHPT, namely percutaneous ethanol injection therapy (PEIT) and a parathyroidectomy (PTx). PEIT is associated with a significant adverse event, adhesion formation. This study was performed to investigate the effect of PEIT on subsequent PTx. Methods. A total of 80 subjects were included in the study. The patients had a diagnosis of RHPT for which surgery was indicated. They were divided according to whether they underwent PEIT (PEIT group) or not (non-PEIT group). The outcomes of PTx following PEIT were evaluated. Results. There were 19 patients in the PEIT group and 61 in the non-PEIT group. The operation time was significantly longer in the PEIT group but no significant differences in the amount of bleeding or frequency of recurrent nerve paralysis were observed. The intact PTH levels immediately following surgery were slightly higher in the PEIT group. The postoperative intact PTH levels were found to be significantly higher in those who received two or more courses of PEIT. The number of patients with an intact PTH level >60 pg/ml on postoperative Day 1 was significantly higher in the PEIT group. Conclusions. These findings suggested that PEIT prior to PTx can affect the subsequent surgical outcome due to associated adhesions and dissemination. For patients with a possibility of either a decreased efficacy or a lack of efficacy for PEIT, it is therefore important to consider PTx from the very beginning of the treatment.

Clinicopathological Analysis of Persistent Hypercalcemia and Hyperparathyroidism After Kidney Transplantation in Long‐Term Dialysis Patients

Deceased donor kidney transplantation in long‐term dialysis patients in Japan has been increasing because of a severe lack of donors. Parathyroid glands of long‐term dialysis patients often show qualitative morphological changes from diffuse to nodular hyperplasia. Only a few studies have reported the clinicopathological analysis of persistent hyperparathyroidism after kidney transplantation in long‐term (>10 years) dialysis patients. This study on consecutive deceased donor kidney transplantation performed from 2002 to 2010 measured biochemical parameters related to bone and mineral disorders and examined parathyroid tissues in parathyroidectomy cases. Thirty‐four subjects (22 males; mean age, 53.8 ± 7.9 years; mean dialysis period, 14.4 ± 4.3 years) were enrolled. Multivariate analysis of potential predictors for the hypercalcemia group at 12 months after transplantation showed that pre‐transplantation and early post‐transplantation calcium and parathyroid hormone levels were significant determinants. Pathological examination showed that a number of glands showed nodular hyperplasia, even in small glands weighing < 100 mg. In long‐term dialysis patients, hyperparathyroidism and hypercalcemia developed at an early stage after transplantation and persisted for a long period (>4 years), with nodular hyperplasia being found even in low‐weight parathyroid glands. Pre‐transplant high calcium and parathyroid hormone levels were the predictors for the prolonged hypercalcemia. Persistent hyperparathyroidism was considered to be caused by remaining nodular hyperplasia, even if the glands were small. Although the best treatment option is to perform a parathyroidectomy in the waiting period before transplantation, we suggest that it be performed in cases with prolonged hypercalcemia of >6 months after transplantation.

Bone mineral density 5 years after parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND Whether bone mineral density (BMD) is improved at 5 years after parathyroidectomy (PTx) for secondary hyperparathyroidism (SHPT) remains unknown. OBJECTIVE To investigate BMD after PTx by dual energy X-ray absorptiometry (DXA). METHODS BMD was measured at the distal 1/3 of the radius (non-shunt side) and at the lumbar supine (L2-L4, lateral view) before and 5 years after PTx in 35 hemodialysis patients who had undergone surgery from April 1994 to May 2004. The data were analyzed retrospectively. RESULTS Intact PTH decreased significantly from 1,100 ± 530 (range: 446 - 2,300) pg/ ml before PTx to 75 ± 68 (2 - 251) pg/ml at 5 years after PTx (p < 0.01). Before PTx, the radial BMD and lumbar BMD were both decreased -3.3 ± 1.9 SD and -1.3 ± 2.4 SD compared with the corresponding normal mean T-score, respectively. Radial BMD increased significantly from 0.522 ± 0.113 g/cm2 before PTx to 0.545 ± 0.114 g/cm2 (p = 0.01) at 5 years after PTx, while the T-score improved to -2.8 ± 2.0 SD. In contrast, lumbar BMD showed no significant change between before (0.734 ± 0.202 g/cm2) and 5 years after PTx (0.746 ± 0.199 g/cm2), and neither did the T-score (-1.1 ± 2.3 SD). None of the patients suffered any fractures during follow up. CONCLUSION These findings indicate that maintaining iPTH at < 300 pg/ml for 5 years after PTx results in an increase of radial BMD in SHPT patients with preoperative BMD levels in the osteoporosis range (below -2.5 SD) according to the WHO, as well as stabilizing lumbar BMD.

A patient with pregnancy-related acute abdomen after hemodialysis for over 18 years.

Because pregnancy is rare in women with end-stage renal disease, dialysis patients have not been reported to present with acute abdominal symptoms related to pregnancy including ectopic pregnancy. A 41-year-old woman treated with hemodialysis for over 18 years was brought to the emergency room at our institution because of acute abdominal pain. Ultrasonography detected an abdominal fluid collection, and her anemia had worsened (hematocrit 18%). Emergency laparoscopic exploration disclosed a hemorrhagic corpus luteum of pregnancy, causing ovarian bleeding on the left. Coagulation of bleeding points was carried out. At this time, pregnancy at 7 weeks of gestation was discovered. After the procedures, hemodialysis frequency was increased to 5 times weekly, and an erythropoietin derivative was administered to maintain a hematocrit above 30%. The patient developed no hypertension. At 33 weeks of gestation, cesarean section was performed because of a decrease in amniotic fluid and frequent late deceleration of the fetal heart rate. A live baby girl weighing 1,422 g was born. The successful pregnancy reflects remarkable progress in dialysis technology. Pregnancy, then, can underlie an acute abdomen in childbearing-age women (14 - 44 years old) undergoing long-term dialysis.

Primary Central Nervous System Post-transplant Lymphoproliferative Disorder Diagnosed by Peripheral Facial Nerve Palsy

Although primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) causes various symptoms depending on the tumor region, there has been no previous report of PCNS-PTLD in the cerebellopontine angle that was diagnosed due to peripheral facial nerve palsy. We herein report a case involving a 62-year-old man with PCNS-PTLD in the cerebellopontine angle who was diagnosed due to peripheral facial nerve palsy. The reduction of immunosuppressive therapy, whole-brain radiotherapy, intrathecal chemotherapy, and rituximab were effective in treating this patient. Physicians should therefore be mindful that PCNS-PTLD can cause peripheral facial nerve palsy in renal transplant recipients.