Combination Therapy of Pembrolizumab plus Axitinib for a Patient on Hemodialysis with Metastatic Renal Cell Carcinoma: A Case Report.

Here, we discuss the safety and management of adverse events associated with pembrolizumab plus axitinib combination therapy for metastatic renal cell carcinoma in patients on hemodialysis. A 76-year-old man was diagnosed with cT3aN0M0 renal cell carcinoma due to gross hematuria. Stereoscopic radiotherapy for metastatic lesions of the ipsilateral kidney was performed 9 years after right laparoscopic radical nephrectomy. Soon after, the patient started to receive hemodialysis due to end-stage renal disease. Further stereoscopic radiotherapy was needed for metastasis of the ipsilateral kidney and lung. Fifteen years after diagnosis, systemic therapy was necessary to control new metastases, such as in the right scapular bone. We selected pembrolizumab plus axitinib combination therapy as the first-line systemic therapy for any risk as defined by the International Metastatic RCC Database Consortium. Although we needed to pay attention to the adverse events unique to hemodialysis, he underwent this combination therapy without any difficulty for 6 months. Here, we report the practice of combination therapy in patients on hemodialysis in light of the literature.

Effect of hematuria on the outcome of immunoglobulin A nephropathy with proteinuria.

BACKGROUND: The relationship between hematuria and histological lesions, the effect of hematuria on response to steroid therapy, and the outcome in patients with immunoglobulin A nephropathy (IgAN) remain undetermined. OBJECTIVES: The aim of this study was to clarify the effect of hematuria on histological findings, response to steroid treatment, and the outcome in IgA nephropathy. PATIENTS AND METHODS: Seventy-five patients with IgAN and proteinuria > 1 g/day and treated with prednisolone were divided into two groups: those with low (≤20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n=55) and those with high (>20/HPF) U-RBC counts (H-RBC group, n=20). Their clinical and histological characteristics, the relationship between hematuria and histological lesions, renal outcomes, and risk factors for progression were compared. RESULTS: Except for U-RBC counts, the clinical and histological findings according to the Oxford classification of the two groups were similar. U-RBC counts were not correlated with active histological lesions. Median proteinuria in both groups decreased soon after starting steroid therapy. Median U-RBC also decreased after starting steroids, and it became similar between both groups at 2 years after treatment. The 20-year renal survival rate was also similar between the H-RBC and the L-RBC group (45.2% versus 58.0%, P=0.5577). Multivariate Cox regression analysis showed that the lower estimated glomerular filtration rate (eGFR) was an independent risk factor for progression. CONCLUSIONS: A higher degree of hematuria at renal biopsy in patients with IgAN was not associated with active pathological lesions, such as cellular and fibro-cellular crescents, resistance to steroid treatment and poor outcome.

Effect of hematuria on the outcome of IgA nephropathy with mild proteinuria.

BACKGROUND: The effects of hematuria on the outcome of IgA nephropathy (IgAN) remain unknown and treatment of IgAN with severe hematuria is controversial. METHODS: Eighty-eight IgAN patients with proteinuria <0.5 g/day and who had not received corticosteroids, immunosuppressive agents, or undergone a tonsillectomy were divided into two groups: (1) patients with low (<20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n = 48); and (2) patients with high (≥20/HPF) U-RBC counts (H-RBC group, n = 40). Clinical and histological findings, renal survival rate and risk factors for progression were analyzed. RESULTS: The male ratio and blood pressure were significantly higher in the L-RBC group. Median proteinuria, mean estimated glomerular filtration rate and histological findings according to Oxford classifications were similar. During the 5 years after renal biopsy, the median amount of proteinuria remained at <0.5 g/day or g/g creatinine in both groups, and the median U-RBC decreased to <10/HPF in both groups without any intensive therapy. The 15-year renal survival rate, estimated using the Kaplan-Meier method, was 100 % in the H-RBC group, but decreased to 83.4 % in the L-RBC group, although it was not significant. The treatment of inhibitors of renin-angiotensin system (RAS inhibitors) decreased the risk for progression by Cox regression analysis (hazard ratio: 0.14, p = 0.027). CONCLUSION: Severe hematuria at the time of biopsy naturally improved without any intensive therapy, and there were no negative effects of hematuria on the outcome of IgAN with mild proteinuria. Its prognosis was relatively good, and the treatment of RAS inhibitors might prevent from progression.

Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single center in Japan.

BACKGROUND: Little is known about the long-term prognosis of patients with IgA nephropathy (IgAN). METHODS: This retrospective cohort analysis evaluated clinical and histological findings at the time of renal biopsy, initial treatment, patient outcomes over 30 years, and risk factors associated with progression in 1,012 patients diagnosed with IgAN at our center since 1974. RESULTS: Of the 1,012 patients, 40.5% were male. Mean patient age was 33±12 years and mean blood pressure was 122±17/75±13 mmHg. Mean serum creatinine concentration was 0.89±0.42 mg/dL, and mean estimated glomerular filtration rate (eGFR) was 78.5±26.2 ml/min/1.73 m2. Mean proteinuria was 1.19±1.61 g/day, and mean urinary red blood cells were 36.6±35.3/high-powered field. Histologically, mesangial hypercellularity was present in 47.6% of patients, endothelial hypercellularity in 44.3%, segmental sclerosis in 74.6%, and tubular atrophy/interstitial fibrosis in 28.8% by Oxford classification. Initial treatment consisted of corticosteroids in 26.9% of patients, renin-angiotensin-aldosterone system inhibitor in 28.9%, and tonsillectomy plus steroids in 11.7%. The 10-, 20-, and 30-year renal survival rates were 84.3, 66.6, and 50.3%, respectively. Tonsillectomy plus steroids dramatically improved renal outcome. Cox multivariate regression analysis showed that higher proteinuria, lower eGFR, and higher uric acid at the time of renal biopsy were independent risk factors for the development of end stage renal disease (ESRD). CONCLUSIONS: IgAN is not a benign disease, with about 50% of patients progressing to ESRD within 30 years despite treatment.

Statins stabilize the renal function of IgA nephropathy.

BACKGROUND: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. METHODS: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. RESULTS: Mean age was 50.5 ± 9.91 years and mean blood pressure was 90.9 ± 10.8 mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71-1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8 ± 22.8 mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7 ± 35.7 mg/dL, low-density lipoprotein cholesterol 151.5 (140.8-172.8) mg/dL, and triglyceride 163.0 (126.3-243.8) mg/dL]. Mild urinary abnormality was observed [proteinuria: 0.50 (0.22-1.29) g/g creatinine, urinary red blood cells 1.0 (0.2-5.0) per high power field]. After 1 year of statin treatment, lipid control was significantly better than at baseline. Proteinuria was not significantly decreased but renal function was improved. eGFR changed from a -5.9% decrease to a 2.4% increase (p = 0.0098). CONCLUSION: Our results indicated that statins stabilized the renal function of IgAN patients independent of their reduction of proteinuria.

Effects of combination therapy with renin-angiotensin system inhibitors and eicosapentaenoic acid on IgA nephropathy.

OBJECTIVE: The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. METHODS: We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. RESULTS: The clinical findings were largely similar between the groups, except for body mass index (24.9±4.5 in the EPA group vs. 21.4±2.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.7±9.0 to 86.4±7.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.2±13.2 to 88.1±7.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). CONCLUSION: We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.