A case of renal sarcoidosis complicated by parotid gland and uterine lesions.

BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.

Sibling cases of gross hematuria and newly diagnosed IgA nephropathy following SARS-CoV-2 vaccination.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has become a major part of the strategy to reduce Coronavirus disease 2019 (COVID-19) numbers worldwide. To date, vaccinations based on several mechanisms have been used clinically, although relapse of existent glomerulonephritis presenting as gross hematuria, and occurrence of de novo glomerulonephritis have been reported. CASE PRESENTATION: We report the first sibling cases newly diagnosed as immunoglobulin A (IgA) nephropathy after the second dose of SARS-CoV-2 vaccination. 15- and 18-year-old men presented with gross hematuria following the second dose of SARS-CoV-2 vaccine (Pfizer, BNT162b2) received on the same day. Pathological findings of each kidney biopsy specimen were consistent with IgA nephropathy. Gross hematuria in both cases spontaneously recovered within several days. CONCLUSIONS: These cases indicate that SARS-CoV-2 vaccination might trigger de novo IgA nephropathy or stimulate its relapse, and also highlight the necessity of understanding the immunological responses to the novel mRNA vaccines in patients with kidney diseases.

A Case of M-Type Phospholipase A2 Receptor-Associated Membranous Nephropathy With IgG4-Positive Cells Infiltration in the Interstitium.

A 70-year-old man was referred to our department for evaluation of nephrotic syndrome. Renal biopsy revealed membranous nephropathy (MN). Immunohistochemical analysis demonstrated IgG4-positive staining in the glomeruli and interstitial cells. The presence of serum anti-phospholipase A2 receptor (PLA2R) antibody and enhanced staining of PLA2R in the glomeruli was noted. Computed tomography unidentified the extrarenal lesions of IgG4-related disease. He was diagnosed with PLA2R-associated MN possibly complicated with IgG4 related kidney disease (IgG4-RKD). Storiform fibrosis, a typical manifestation of IgG4-RKD, was not apparent. We herein describe a case of serologically and histologically confirmed PLA2R-associated MN with IgG4+ cell infiltration into the interstitium without any signs of IgG4-RD.

Pembrolizumab-associated nephrotic syndrome recovered from transient hemodialysis in a patient with lung cancer.

A 70-year-old man diagnosed with lung adenocarcinoma was referred to our department for an evaluation of acute onset of nephrotic syndrome with acute kidney injury (AKI) after the 7th course of pembrolizumab treatment. Renal biopsy could not be performed, because he needed anticoagulation therapy for venous thrombosis. Pembrolizumab was discontinued, and prednisolone was started. Hemodialysis was also started, because oliguria was not resolved, and dyspnea due to pulmonary congestion appeared even with the high dose of diuretics. Hemodialysis was successfully withdrawn within 5-week duration because of renal function recovery and increase of urine volume. Complete remission was achieved 4 months after initiating prednisolone. He has never experienced hemodialysis again and remains remission of nephrotic syndrome even the dose of prednisolone was tapered for 8 months. Renal pathology in the current case was uncertain. However, minimal change disease seemed to be a plausible cause of nephrotic syndrome with AKI because of a good response to steroid therapy and acute onset of nephrotic syndrome. In addition, renal pathology in all of the reported cases of pembrolizumab-associated nephrotic syndrome with AKI was minimal change disease. Our case shows for the first time that renal function could be reversible with prednisolone in pembrolizumab-associated nephrotic syndrome with severe AKI even after progression of renal failure which needs dialysis.

Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: A retrospective study.

BACKGROUND: Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients. METHODS: We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors. RESULTS: A total of 455 patients were treated with cisplatin during the period. Of these, 34 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 43.1± 20.1%, respectively; P = 0.010]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 64%, respectively; P = 0.026). CONCLUSIONS: DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients.

A Reversible Gastric Uptake of Bone Scintigraphy in a Patient with Hypercalcemia.

Hypercalcemia is a severe complication in cases of vitamin D intoxication that can result in metastatic calcification. We herein report a female case with hypercalcemia due to eldecalcitol administration associated with the increased uptake of technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) as the bone-scanning agent in the stomach. A histologic assessment using biopsy specimens identified metastatic calcification of the stomach. After the normalization of serum calcium levels, the gastric uptake of 99mTc-HMDP disappeared. This case indicates the usefulness of bone scintigraphy with 99mTc-HMDP to detect visceral metastatic calcification and to monitor its therapeutic effects in patients with hypercalcemia.

Carbohydrate antigen 19-9 is significantly elevated in autosomal dominant polycystic kidney disease.

AIM: Liver cysts are the most common extrarenal manifestation in patients with autosomal dominant polycystic kidney disease (ADPKD). Carbohydrate antigen 19-9 (CA19-9) is generally used as a marker for biliopancreatic malignancies, although CA19-9 levels in patients with ADPKD are largely unknown. METHODS: A prospective observational study of 53 ADPKD patients and 83 non-ADPKD control subjects was performed. The serum levels of CA19-9 were studied to evaluate the association with clinical parameters and liver cysts. RESULTS: The serum CA19-9 levels were significantly higher in the ADPKD group than in the control group (32.9 U/mL vs. 9.8 U/mL, respectively, P < 0.001). The serum CA19-9 levels in the ADPKD group were positively correlated with the mean blood pressure (rho = 0.335, P < 0.05), gamma-glutamyl transferase (GTP) levels (rho = 0.541, P < 0.001), the largest cyst size (rho = 0.536, P < 0.001) and the liver cyst volume (rho = 0.682, P < 0.001). Multiple regression analyses showed that the gamma-GTP levels (P < 0.001) and the liver cyst volumes (P < 0.001) were independent predictors for serum CA19-9 levels. CONCLUSIONS: Serum CA19-9 levels are significantly elevated and appear to be dependent on the gamma-GTP levels and the volume of liver cysts in patients with ADPKD. Our findings indicate that the measurement of the baseline CA19-9 level in each patient with ADPKD may be useful for the interpretation of the value and the differential diagnosis of liver diseases, particularly the liver cyst infection.

Hypokalemia-associated paralysis and metabolic acidosis in a patient with bilateral ureterosigmoidostomy.

Ureterosigmoidostomy is a urological intervention performed to treat various conditions such as invasive bladder cancer, bladder exstrophy, vesicovaginal fistula, or urethral trauma. However, this intervention may lead to several metabolic complications. Here, we report an interesting case with quadriparesis and intestinal paralysis resulting from severe hypokalemia (the serum potassium level, 1.8 mEq/L) and hyperchloremic metabolic acidosis [pH 6.927 and the arterial bicarbonate level, 8.0 mEq/L] in a 65-year-old man who had undergone bilateral ureterosigmoidostomy for bladder cancer 16 years earlier. The abdominal computed tomography scan also showed that massive fluid consisting of the mixture of the diverted urinary stream and feces was accumulated in the dilated distal colon. The treatment with intravenous potassium and sodium bicarbonate administration combined with the drainage of the diverted urinary stream from the distal colon resulted in the restoration of hypokalemia and acidosis followed by the improvement of quadriparesis and intestinal paralysis. The underlying mechanism and the treatment of metabolic complications after ureterosigmoidostomy are briefly discussed.

Anti-cancer agent-induced nephrotoxicity.

Patients with cancer are frequently exposed to risk of renal injuries associated with disease-related or iatrogenic causes. Nephrotoxicity is a potential adverse effect of anti-cancer agents and may result in a variety of functional abnormalities, including glomerular or tubular dysfunction, hypertension and disturbance of the renal endocrine function. In this review article, we comprehensively discuss the incidence, clinical presentation, prevention and management of anti-cancer agent-induced renal dysfunction. We focus on both relatively new anti-cancer agents (bevacizumab, gefitinib, gemcitabine, imatinib, rituximab and trastuzumab) and traditional agents (cisplatin, methotrexate, ifosfamide and taxanes) to cover a selection of the most frequently used anti-cancer agents. Increased understanding of the mechanism of renal injury by these agents is considered to be important for developing novel anti-cancer agents that have far fewer adverse effects on kidneys.

Acquired Fanconi syndrome in patients with Legionella pneumonia.

BACKGROUND: Hyponatremia is often observed in patients with Legionella pneumonia. However, other electrolyte abnormalities are uncommon and the mechanism remains to be clarified. CASE PRESENTATION: We experienced two male cases of acquired Fanconi syndrome associated with Legionella pneumonia. The laboratory findings at admission showed hypophosphatemia, hypokalemia, hypouricemia and/or hyponatremia. In addition, they had the generalized dysfunction of the renal proximal tubules presenting decreased tubular reabsorption of phosphate (%TRP), increased fractional excretion of potassium (FEK) and uric acid (FEUA), low-molecular-weight proteinuria, panaminoaciduria and glycosuria. Therefore, they were diagnosed as Fanconi syndrome. Treatment for Legionella pneumonia with antibiotics resulted in the improvement of all serum electrolyte abnormalities and normalization of the %TRP, FEK, FEUA, low-molecular-weight proteinuria, panaminoaciduria and glycosuria, suggesting that Legionella pneumophila infection contributed to the pathophysiology of Fanconi syndrome. CONCLUSION: To the best of our knowledge, this is the first report demonstrating Fanconi syndrome associated with Legionella pneumonia.

Inflammatory factors for hypoalbuminemia in Japanese peritoneal dialysis patients.

AIM: Hypoalbuminaemia is a common complication of peritoneal dialysis (PD), and the leakage of albumin through peritoneal membrane may be a principal reason for hypoalbuminaemia. However, the relationship between peritoneal inflammation, peritoneal transport properties and hypoalbuminaemia has not been fully elucidated. METHODS: A cross-sectional study was performed on 76 Japanese PD patients who had been using a low-glucose PD solution and icodextrin. Systemic inflammatory markers of C-reactive protein (CRP) and serum interleukin-6 (IL-6), peritoneal effluent markers of dialysate IL-6 and CA125, the dialysate-to-plasma ratio of creatinine (D/Pcr) and the dialysate protein concentration were measured and examined for their relationship with hypoalbuminaemia. RESULTS: There was a significant positive correlation between serum IL-6 and dialysate IL-6, mean dialysate IL-6 being significantly higher than mean serum IL-6, suggesting that intraperitoneal inflammation was a principal origin of systemic inflammation. Both serum and dialysate IL-6 were significantly correlated with serum albumin (r= -0.25, P<0.05 and r=-0.32, P<0.01, respectively). Dialysate IL-6 was significantly correlated with D/Pcr and the dialysate protein concentration, and there was a significantly positive association between D/Pcr and the dialysate protein concentration. Dialysate CA125, which is argued to be a marker of mesothelial cell mass in this study, was positively correlated with D/Pcr and the dialysate protein concentration. The dialysate protein, dialysate IL-6 and dialysate CA125 all increased according to the peritoneal transport rate defined by D/Pcr. A multiple-regression analysis showed that serum albumin was independently associated with the age, D/Pcr and serum IL-6. CONCLUSION: Hypoalbuminaemia was attributable to both the increased peritoneal permeability and systemic inflammation, and intraperitoneal inflammation might contribute to developing these complications.

Survey of the effects of a column for adsorption of ß2-microglobulin in patients with dialysis-related amyloidosis in Japan.

Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of ß2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of ß2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients.

Simplified nutritional screening tools for patients on maintenance hemodialysis.

BACKGROUND: Malnutrition is a prevalent complication in patients on maintenance hemodialysis. Nutritional screening tools may be useful to identify those patients at nutritional risk from among hundreds of hemodialysis patients in a large facility. OBJECTIVE: We tested several simplified nutritional screening tools on hemodialysis patients to validate the potential application of the tools. DESIGN: The simplified nutritional screening tools were chosen from references published between 1985 and 2005. Nutritional assessments, including history taking, and anthropometric and biochemical measurements were performed on 422 hemodialysis patients. These results were applied to obtain the score of each nutritional screening tool and the malnutrition-inflammation score (MIS), a comprehensive nutritional assessment tool, as the reference standard. The usefulness of each nutritional screening tool for identifying nutritional risk was assessed by comparison with the MIS value and various individual nutritional measures. RESULTS: Five reliable nutritional screening tools were found by the literature search. Among them, the geriatric nutritional risk index (GNRI) was considered to be the most accurate in identifying hemodialysis patients at nutritional risk, because the area under the receiver operating characteristic curve generated with the MIS value was the largest. The GNRI showed a significantly negative correlation with the MIS (r=-0.67, P<0.0001), and the most accurate GNRI cutoff to identify a malnourished patient according to the MIS was <91.2. The GNRI's sensitivity, specificity, and accuracy of <91.2 in predicting malnutrition according to the MIS were 0.730, 0.819, and 0.787, respectively. CONCLUSION: The GNRI was the simplest and most accurate risk index for identifying hemodialysis patients at nutritional risk according to the MIS.

Ultrapure dialysate reduces plasma levels of beta2-microglobulin and pentosidine in hemodialysis patients.

BACKGROUND: beta2-Microglobulin (beta2MG) and carbonyl stress are reported to contribute to the development of dialysis-related amyloidosis. The aim of this study was to determine whether the purity of dialysate affects plasma levels of beta2MG and pentosidine (a surrogate marker of carbonyl stress) in hemodialysis patients. METHODS: Sixteen patients on hemodialysis with a polysulfone membrane participated in this study. We switched the dialysate from conventional dialysate (endotoxin level 0.055-0.066 endotoxin units (EU)/ml) to ultrapure dialysate (endotoxin level <0.001 EU/ml), followed patients for 6 months, and then switched back to conventional dialysate once again. Plasma levels of beta2MG, pentosidine, CRP and interleukin-6 (IL-6) were determined before the switch to ultrapure dialysate, 1 and 6 months after the switch to ultrapure dialysate, and 1 month after the switch back to conventional dialysate. RESULTS: The switch from conventional to ultrapure dialysate significantly decreased plasma levels of beta2MG, from 30.1 +/- 1.4 to 27.1 +/- 1.4 mg/dl (p < 0.05) and pentosidine, from 1,535.8 +/- 107.5 to 1,267.6 +/- 102.9 nmol/l (p < 0.01) after 1 month of use. The change of dialysate also significantly decreased plasma levels of CRP, from 0.28 +/- 0.09 to 0.14 +/- 0.05 mg/dl (p < 0.05) and IL-6, from 9.4 +/- 2.7 to 3.5 +/- 0.8 pg/ml (p < 0.01) over the 1-month period. These changes in plasma levels of beta2MG, pentosidine, CRP and IL-6 were maintained over 6 months after switching to ultrapure dialysate and returned to basal levels by switching back to a conventional dialysate. CONCLUSIONS: Ultrapure dialysate decreases plasma levels of beta2MG, pentosidine and inflammatory markers in hemodialysis patients. The use of ultrapure dialysate might be useful in preventing and/or treating complications of dialysis, such as dialysis-related amyloidosis, atherosclerosis and malnutrition.