Clinical relevance of postoperative proteinuria for prediction of early renal outcomes after kidney transplantation

Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. Methods: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2–3 weeks postoperatively), and 3–6 months postoperatively. Results: The median age of the patients was 51 years (interquartile range, 43–59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. Conclusion: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

The presence of simple renal cysts is associated with an increased risk of albuminuria in young adults

Background/Aims@#The prevalence of simple renal cysts increases with age; however, they are occasionally found in adults aged < 40 years. This cross-sectional study evaluated the clinical significance of simple cysts in young adults, focusing on their associations with hematuria and albuminuria. @*Methods@#Adults aged < 40 years who underwent comprehensive medical examination between January 2005 and December 2013 were included. Simple renal cysts were identified by ultrasonography. @*Results@#Renal cysts were found in 276 of the 5,832 subjects (4.7%). Subjects with medullary sponge kidney (n = 1) or polycystic kidney disease (n = 5) were excluded. A single cyst and multiple cysts were found in 234 (4.0%) and 42 (0.7%) subjects, respectively. Age, high systolic blood pressure, and history of hypertension were independent risk factors for the presence of simple cysts. Simple cysts were not associated with an increased prevalence of hematuria. However, subjects with cysts showed a higher prevalence of albuminuria than those without (11.3% vs. 4.5%, p < 0.001). Multivariate analysis revealed that the existence of simple renal cysts was associated with a 2.30-fold increased prevalence of albuminuria (95% confidence interval, 1.512 to 3.519; p < 0.001) independent of other risk factors. @*Conclusions@#In young adults, the presence of simple renal cysts was independently associated with an increased prevalence of albuminuria. The causal relationship needs to be elucidated in further studies.

Effects of percutaneous angioplasty on kidney function and blood pressure in patients with atherosclerotic renal artery stenosis

BACKGROUND: Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS. METHODS: From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of ‘kidney function improvement’ or ‘hypertension improvement’ after PTA/S were classified as responders. RESULTS: Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10–45) mL/min/1.73 m² to 41 (IQR, 16–67) mL/min/1.73 m² at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150–164) mmHg to 140 (IQR, 131–148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004). CONCLUSION: PTA/S might improve BP control and kidney function in patients with ARAS presenting with high-risk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.

Crystalline podocytopathy and tubulopathy without overt glomerular proteinuria in a patient with multiple myeloma

Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain–secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury.

Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis

Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.

A Case of Light Chain Deposition Disease in a Patient with Diabetes and Nodular Glomerulosclerosis / 대한내과학회지

A 50 year-old male with a 10-year history of diabetes was admitted to the hospital for edema and foamy urine. At the time of admission, serum creatinine was 1.99 mg/dL and 24 h urine protein levels were 4.0 g/day. Renal biopsy showed nodular glomerulosclerosis. Immunofluorescence demonstrated the presence of kappa light chains along the glomerular and tubular basement membrane. Electron microscopy showed granular electron-dense deposits along the glomerular subendothelium and tubular basement membrane. Serum protein electrophoresis was negative for a monoclonal spike; however, urine protein electrophoresis demonstrated a monoclonal spike. Bone marrow examination was compatible with multiple myeloma and the patient was diagnosed with light-chain deposition disease associated with multiple myeloma. This report stresses the significant challenges that occur when diagnosing light-chain deposition disease in kidneys of patients with long standing diabetes, and discusses previously reported cases of light-chain deposition disease in Korea.

The impact of early and late acute rejection on graft survival in renal transplantation

BACKGROUND: Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR. We investigated whether the timing of acute rejection (AR) influences graft survival, and analyzed the risk factors for EAR and LAR. METHODS: We performed a retrospective cohort study involving 709 patients who underwent kidney transplantation between 2000 and 2009 at the Samsung Medical Center, Seoul, Korea. Patients were divided into three groups: no AR, EAR, and LAR. EAR and LAR were defined as rejection before 1 year and after 1 year, respectively. Differences in graft survival between the three groups and risk factors of graft failure were analyzed. RESULTS: Of the 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both by log-rank test). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90-5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65-10.69) were significantly related to graft failure. When we set LAR as standard and compared it with EAR, there was no statistical difference between EAR and LAR (P=0.21). CONCLUSION: AR, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.

A case of Fanconi syndrome accompanied by crystal depositions in tubular cells in a patient with multiple myeloma

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.

A Case of Lung Disease and Vertebral Osteomyelitis Due to Nontuberculous Mycobacteria in a Kidney Transplant Recipient / 대한내과학회지

Nontuberculous mycobacteria (NTM) infections in kidney transplant recipients (KTR) are rare. We describe here a 52-year-old female with vertebral osteomyelitis caused by NTM, who received a kidney transplant 5 years earlier. She had been diagnosed with NTM lung disease 1 year prior. NTM therapy was delayed due to esophageal candidiasis. Mycobacterium intracellulare was isolated from sputum and bone tissue. The pattern of drug-susceptibility testing in both specimens was identical. NTM vertebral osteomyelitis due to direct inoculation is rare, and was in this case a disseminated NTM disease. The subjective symptoms resolved after 4 months of NTM treatment. This suggests that early NTM treatment is important for KTRs who have NTM disease during immunosuppressive therapy.

Two cases of idiopathic membranous nephropathy treated with rituximab

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome, and has been reported as a cause of idiopathic primary glomerulonephropathy in up to 90% of patients. However, the treatment options remain controversial. We report two cases of idiopathic membranous nephropathy that were treated with rituximab. A 54-year-old man and a 64-year old man were admitted for rituximab therapy. They had previously been treated with combinations of immunosuppressive agents including cyclophosphamide, cyclosporine, mycophenolate, and steroids. However, the patients' heavy proteinuria was not resolved. Both patients received rituximab therapy, 2 weeks apart. After several months of follow-up and a second round of rituximab treatment for each patient, their proteinuria decreased and partial remission of disease was achieved in both patients.

Patients with Persistent New-Onset Diabetes after Transplantation Have Greater Weight Gain after Kidney Transplantation

The purpose of the present study was to evaluate the difference in BMI pattern between patients with persistent new-onset diabetes after transplantation (P-NODAT) and without new-onset diabetes after transplantation (N-NODAT) in a retrospective matched case-control (1:3) analysis. Thirty-six patients who developed P-NODAT were identified among 186 adult renal transplant recipients with no evidence of pretransplant diabetes mellitus who underwent kidney transplantation from September 1997 to March 2008 and were treated with a triple regimen including tacrolimus. The controls were selected to match the patients for pretransplant BMI, age at transplantation (+/- 5 yr), and date of transplantation (+/- 12 months). Finally, 20 P-NODAT patients and 60 N-NODAT patients were selected. The pre- and posttransplant BMI data were collected every 16 weeks for up to 80 weeks. The clinical characteristics did not differ between the P-NODAT group and N-NODAT group. BMI increased faster in the P-NODAT group than in the N-NODAT group. The mixed-model analysis showed that patients with P-NODAT exhibited a faster increase in BMI. P-NODAT is associated with posttransplant weight gain. The risk of P-NODAT should be considered in patients with rapid weight gain after transplantation.

Intravenous albumin for the prevention of contrast-induced nephropathy in patients with liver cirrhosis and chronic kidney disease undergoing contrast-enhanced CT

BACKGROUND: The purpose of this study was to evaluate the incidence of contrast-induced nephropathy (CIN), and the effect of intravenous albumin for prophylaxis of CIN in patients with liver cirrhosis (LC) and chronic kidney disease (CKD). METHODS: We conducted a retrospective study of 81 subjects with LC and CKD (estimated glomerular filtration rate (eGFR) or =25% or > or =0.5mg/dL in serum creatinine level. RESULTS: Overall, CIN developed in three patients (3.7%). Of the 81 subjects, 43 received sodium bicarbonate solution and 38 received albumin. Both groups were comparable with regard to age, sex, diabetes mellitus, and baseline eGFR. The albumin group showed a significantly poorer liver function profile. CIN incidence did not differ significantly between the groups: it occurred in one (2.3%) of the 43 subjects receiving sodium bicarbonate and two (5.3%) of the 38 subjects receiving albumin (P=0.6). However, the albumin group showed a significantly smaller increase in body weight (P=0.03). CONCLUSION: The incidence of CIN in patients with LC and CKD undergoing contrast-enhanced CT after preventive measures was relatively low. The incidence of CIN was not significantly different between sodium bicarbonate and albumin groups.

Giant Splenic Artery Pseudoaneurysm Presenting with Acute Kidney Injury / 대한내과학회지

Splenic artery pseudoaneurysm is a rare, but potentially lethal, vascular lesion. The mortality rate may be 75-90%, if the aneurysm ruptures. The risk for rupture of an untreated splenic artery pseudoaneurysm is about 37%. Hence, early diagnosis and prompt surgical intervention are vital to improve survival. However, vague symptoms make early diagnosis difficult. We report here a case of a giant splenic artery pseudoaneurysm presenting with acute kidney injury. The patient had been treated previously for infective endocarditis, and after 4 months, acute kidney injury developed. Imaging studies revealed a giant splenic artery pseudoaneurysm. Splenectomy and distal pancreatectomy were performed. After surgery, renal function was improved.

Giant Splenic Artery Pseudoaneurysm Presenting with Acute Kidney Injury / 대한내과학회지

Splenic artery pseudoaneurysm is a rare, but potentially lethal, vascular lesion. The mortality rate may be 75-90%, if the aneurysm ruptures. The risk for rupture of an untreated splenic artery pseudoaneurysm is about 37%. Hence, early diagnosis and prompt surgical intervention are vital to improve survival. However, vague symptoms make early diagnosis difficult. We report here a case of a giant splenic artery pseudoaneurysm presenting with acute kidney injury. The patient had been treated previously for infective endocarditis, and after 4 months, acute kidney injury developed. Imaging studies revealed a giant splenic artery pseudoaneurysm. Splenectomy and distal pancreatectomy were performed. After surgery, renal function was improved.

Slowly Progressing Thrombotic Microangiopathy during Two Years of Treatment with Sunitinib / 대한신장학회지

A 75-year-old man with mild renal impairment was started on sunitinib for a metastatic gastrointestinal stromal tumor. After 7 months of this therapy, proteinuria became aggravated. Serum creatinine concentration was increased from 1.34 to 2.57 mg/dL 24 months after sunitinib administration. Hematologic features of thrombotic microangiopathy (TMA) were absent. Renal histology revealed endothelial swelling and plasmatic insudation of the glomeruli. Proteinuria and renal function improved after discontinuation of sunitinib. Our experience suggests that TMA associated with sunitinib can be diverse in onset and severity, and that the hematologic features of TMA may be absent.

Urinary Angiotensinogen Excretion and Intrarenal Angiotensinogen Expression in Minimal Change Disease Patients / 대한신장학회지

PURPOSE: Urinary angiotensinogen (AGT) has been reported as an important marker reflecting the activity of intrarenal renin-angiotensin system (RAS) in chronic glomerulonephritis patients. We investigated urinary AGT excretion and intrarenal AGT expression in patients with minimal change disease (MCD). METHODS: In 20 patients with biopsy-proven MCD, urinary and plasma AGT was measured using a sandwich ELISA and intrarenal AGT expression was measured with immunohistochemistry. Urine samples from normal healthy volunteers and patients with biopsy-proven thin basement membrane disease (TBM) were used as control groups. RESULTS: MCD patients showed a wide range of natural logarithm of the urinary AGT/creatinine [ln (urinary AGT/Cr)] and the ln (urinary AGT/Cr) was higher in MCD patients compared with normal controls and TBM controls (normal control vs. TBM vs. MCD, 1.2+/-0.25 vs. 0.9+/-0.34 vs. 3.2+/-0.40). Intrarenal AGT expression was diverse in MCD patients (intrarenal AGT, arbitrary unit, 27.39-78.52 in TBM, 0.00-145.80 in MCD). Ln (urinary AGT/Cr) did not show a direct correlation with intrarenal AGT expression, plasma AGT, or urinary protein/creatinine ratio. CONCLUSION: Urinary AGT excretion and intrarenal AGT expression are enhanced in some MCD patients, suggesting that intrarenal RAS is activated in these patients.

A Case of Crescentic Glomerulonephritis Superimposed on Membranous Glomerulopathy / 대한신장학회지

Membranous glomerulopathy (MGN) is a common cause of nephrotic syndrome in adults. Renal failure gradually develops in patients with MGN and crescentic glomerulonephritis (CGN) superimposed on MGN is a rare cause of acute renal failure. In most cases patients showed nephrotic syndrome with acute renal failure. We report a 33-year-old woman with azotemia but with no other symptoms such as nephrotic syndrome she had been diagnosed to have MGN 15 months before. There seemed to be no other cause of azotemia. Renal biopsy was performed and revealed CGN on existing MGN. She was treated with immunosuppression treatment and azotemia was improved. When unexplained azotemia develops in patients with MGN, we should promptly investigate superimposed conditions including CGN. In CGN superimposed on MN, a potentially reversible condition with appropriate immunosuppression therapy should be considered.

Three Cases of Minimal Change Nephrotic Syndrome in Patients with Type 2 Diabetes / 대한신장학회지

Diabetic nephropathy is a common and serious complication of diabetes characterized by persistent proteinuria, hypertension and a progressive decline of renal function. However, non-diabetic renal disease can be present in diabetic patients and differential diagnosis of treatable disease is important. Minimal change nephrotic syndrome is characterized by normal light microscopic finding and effacement of foot process in electron microscope, but foot process effacement is not specific and it can be present in the glomeruli of the most glomerulopathy including diabetic nephropathy. Therefore, pathologic diagnosis of minimal change nephrotic syndrome combined with diabetic nephropathy is very difficult. However, we could exclude other glomerulopathy and diagnose minimal change nephrotic syndrome by clinical features in three type 2 diabetic patients with diabetic nephropathy and have successfully treated with corticosteroid.

Characteristics of Pneumonia and Clinical Significance of Atelectasis in Patients with Chronic Kidney Disease Stage 5 / 대한신장학회지

PURPOSE: Pneumonia is a common condition in patients with chronic renal insufficiency, and the condition is closely associated with high mortality and hospitalization rate in such patients. However, limited information is available about the clinical course of pneumonia in these patients, particularly in those with coexistent pulmonary atelectasis. We studied the characteristics of pneumonia as well as the clinical significance of pulmonary atelectasis in patients with chronic renal insufficiency. METHODS: We retrospectively reviewed the medical records of 25 patients with chronic renal insufficiency that were diagnosed as having pneumonia with atelectasis. The clinical, laboratory and radiological findings in these patients were examined. We also assessed the severity of atelectasis in these patients and compared the clinical courses of patients with different grades of atelectasis. RESULTS: The mean age of the patients was 71 years, and 15 of the 25 patients (60%) had diabetes. On chest computed tomography, the incidence of lobar infiltration, atelectasis, and pleural effusion was 75%, 64%, and 56%, respectively. The incidences of severe pneumonia and death tended to increase with the severity of atelectasis; however the increase was not statistically significant. The incidence of recurrence of pneumonia was significantly higher in patients with severe atelectasis than that in those without atelectasis. CONCLUSION: The incidence of severe pneumonia and the mortality rate tended to be higher in patients with severe atelectasis than in those without atelectasis. In addition, severe atelectasis was associated with the recurrence of pneumonia in patients with chronic renal insufficiency.

Risk Factors for New Onset Diabetes after Transplantation among Renal Transplant Recipients Treated with Tacrolimus / 대한신장학회지

PURPOSE: This study was conducted to identify risk factors for new onset diabetes after transplantation (NODAT) among renal transplant recipients treated with tacrolimus-based immunosuppressant. METHODS: We selected renal transplant recipients who underwent surgery at Samsung Seoul Hospital between May 2001 and July 2009. Exclusion criteria were as follows: recipients years: RR=4.36, 95% CI 2.00-9.49), family history of DM (RR=1.62, 95% CI 1.12-2.34) and polyomavirus infection (RR=1.40, 95% CI 1.08-1.81). CONCLUSION: The risk factors for NODAT among renal transplant recipients treated with tacrolimus-based regimen were age (>45 years old), family history of DM and polyomavirus infection.