Clinical and Histopathological Analysis of the Kidney Biopsies of 2,450 Patients seen over 30 Years at Chungnam National University Hospital / 대한내과학회지

BACKGROUND/AIMS: This study evaluated the clinical characteristics of patients who underwent kidney biopsies, and the relative changes in pathological diagnosis, according to time periods over the last 30 years (1981-2010). METHODS: This study included 3,051 patients who were older than 15 years and underwent kidney biopsies at Chungnam University Hospital between January 1981 and December 2010. For analysis, the patients were grouped into three time periods: I (1981-1990), II (1991-2000), and III (2001-2010). We reviewed the available medical records of 2,450 patients and analyzed the changes in their clinical characteristics over time. RESULTS: The mean patient age was 35.9 (range 15-91) years and the male-to-female ratio was 1.3:1. The most common indication for a kidney biopsy was an asymptomatic urinary abnormality (64.2%) and the proportion with this indication increased significantly over time (p < 0.001). Primary glomerular diseases comprised 65.4% of all pathological diagnoses, followed by secondary (13.6%) and hereditary (12.5%) glomerular diseases. The proportion of primary glomerular diseases decreased significantly with time (p < 0.001), while the proportions of secondary and hereditary glomerular diseases increased correspondingly (p < 0.001). IgA nephropathy was the most common pathological diagnosis (36.7%) overall. The proportion of IgA nephropathy increased significantly with time (p < 0.001), while minimal change disease and acute post-streptococcal glomerulonephritis decreased significantly (p < 0.001 and p = 0.013, respectively). CONCLUSIONS: The results demonstrated that the clinical indications and pathological diagnoses in patients who underwent kidney biopsies changed significantly over the last 30 years.

Nondiabetic kidney diseases in type 2 diabetic patients

BACKGROUND: The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient. METHODS: Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010. RESULTS: The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline inrena lfunction (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P = 0.008).Group II had the lowest baseline estimated glomerular filtration rate (P = 0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, P < 0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P = 0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P = 0.032). CONCLUSION: Renal biopsy should be recommended for type 2 diabetic patients with a typical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy.

Severe Hypernatremia by Excessive Bamboo Salt Ingestion in Healthy Young Woman

Severe hypernatremia is an important electrolyte disorder that has serious effects. The patient had no medical history. A. 20-year-old ingested bamboo salt for digestion and weight reduction according to the folk remedies posted on an internet website. She presented with vomiting and diarrhea over ten times per day. Her initial serum sodium concentration was 174mEq/L. Her symptoms improved rapidly with hypotonic saline infusion. She recovered completely without any sequelae in three days. Severe hypernatremia in a normal young adult with clear consciousness and normal renal function has not been reported in Korea yet. So we report a case of severe hypernatremia by excessive bamboo salt ingestion in healthy young woman.

Hyperammonemia in a Patient with Late-Onset Ornithine Carbamoyltransferase Deficiency

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.

A Case of Urine Leakage: An Unusual Complication after Renal Biopsy / 전남의대학술지

Renal biopsy is a crucial method in the diagnosis and treatment of acute renal failure of unknown origin, nephrotic syndrome, suspicious interstitial nephritis, and glomerulonephritis as a possible cause of hematuria or proteinuria. Complications occur in 2% to 8% of patients after percutaneous renal biopsy. Complications include gross hematuria, perirenal hematoma, arteriovenous fistula, aneurysm, injury of other organs, and urine leakage. Urine leakage as a complication after kidney biopsy is rare. We experienced a case of urine leakage into the intra-abdominal cavity after renal biopsy.

Hydration Status and Clinical Features in Patients with End-Stage Renal Disease on Regular Hemodialysis / 대한신장학회지

PURPOSE: Maintenance of the normal hydration state is one of the major purposes of hemodialysis therapy in patients with end-stage renal disease. Overhydration is an important and independent predictor of mortality in patients with end-stage renal disease on regular hemodialysis. BCM (body composition monitor, FMC, Germany) reliably enables quantitative assessment of hydration status and body composition. The aims of this study were to investigate the relationship between hydration status and clinical features and the risk factors of overhydration. METHODS: We measured hydration status and body composition of total 72 patients with end-stage renal disease on regular hemodialysis by BCM from June, 2009 to September, 2009. We also reviewed the clinical characteristics and laboratory findings and comorbidities retrospectively. RESULTS: The hydration status measured by BCM was correlated well with interdialytic weight gain after 48 hours and 72 hours from last hemodialysis treatment (r=0.42 p or =20%) and control patients (relative hydration status <20%). In overhydrated patients, serum iron level was lower than control patients 48 hrs after last hemodialysis (p<0.05). CONCLUSION: This cross-sectional study showed that hydration status measured by BCM was correlated well with interdialytic weight gain although there was no significant clinical difference between overhydrated and control patients with end-stage renal disease on regular hemodialysis.

A Case of Urine Leakage: An Unusual Complication after Renal Biopsy / 전남의대학술지

Renal biopsy is a crucial method in the diagnosis and treatment of acute renal failure of unknown origin, nephrotic syndrome, suspicious interstitial nephritis, and glomerulonephritis as a possible cause of hematuria or proteinuria. Complications occur in 2% to 8% of patients after percutaneous renal biopsy. Complications include gross hematuria, perirenal hematoma, arteriovenous fistula, aneurysm, injury of other organs, and urine leakage. Urine leakage as a complication after kidney biopsy is rare. We experienced a case of urine leakage into the intra-abdominal cavity after renal biopsy.

Prognostic Factors of Acute Renal Failure Patients Treated with Continuous Renal Replacement Therapy / 대한신장학회지

PURPOSE: Continuous renal replacement therapy (CRRT) has been used widely for treating critically ill patients with acute renal failure (ARF). We performed this study to identify predictors of mortality in critically ill ARF patients treated with CRRT. METHODS: We analyzed the data of 128 patients who were treated with continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodiafiltration (CVVHDF) from May, 2002 to March, 2008. We compared the clinical data of survivors with non-survivors. RESULTS: On univariate analyses of prognostic factors of patients treated with CVVHDF, APACHE II scores (p=0.004), prothrombin time (INR) (p=0.033) and the number of inotropics used (p=0.005) were significantly lower in survivors than those of non-survivors. MAP (p=0.027), diastolic BP (p=0.015) and fibrinogen level (p=0.007) were significantly higher in survivors than those of non-survivors. Multivariate analysis revealed that APACHE II scores and fibrinogen level were the independent factors for the prediction of mortality. And on univariate analyses of prognostic factors of patients treated with CVVH, APACHE II scores (p=0.002) and the number of inotropics used (p=0.006) were significantly lower in survivors than in non-survivors. MAP (p=0.03), systolic BP (p=0.02) and diastolic BP (p=0.03) were significantly higher in survivors than in non-survivors. Multivariate analysis also revealed that APACHE II scores was the only independent factor for the prediction of mortality. CONCLUSION: This study showed that the independent prognostic factor for mortality in ARF patients treated with CRRT was the APACHE II score.

A Case of Septic Pulmonary Embolism in an End-Stage Renal Failure Patient with Infected Arterio-venous Graft for Hemodialysis / 대한신장학회지

Septic pulmonary embolism (SPE) is different from non-infectious thromboembolism in that it causes pulmonary arterial obstruction and inflammation by infectious emboli from various sources. There are increased risks of SPE in patients with chronic kidney disease because of decreased immunity and frequent venous puncture with the use of indwelling venous catheters or arterio-venous graft (AVG). However, SPE related with AVG infection in end-stage renal failure patient is very rare. Recently, we experienced a typical case of septic pulmonary embolism occurring in a 57-year-old man with infected AVG during hemodialysis. The patient had started hemodialysis 10 years ago due to diabetic end stage renal failure. Due to functional failure of the arterio-venous fistula, hemodialysis had been performed through an AVG on the upper left arm 3 years before admission.

C-phycocyanin Attenuates Renal Inflammation and Fibrosis in UUO Mice / 대한신장학회지

PURPOSE: It has been reported that Spirulina, a blue-green algae with potent antioxidant properties, affords significant protection against inflammation and fibrosis in the liver in vivo. The aim of the present study was to establish the possible protective role of C-phycocyanin, one of the active ingredients of Spirulina, in an experimental model of fibrosis in the kidney. METHODS: The study was carried out using male C57BL6 mice. Mice were divided into the following four groups: sham-operated group; C-phycocyanin (PC)-treated sham group; unilateral ureteral obstruction (UUO) group; and PC with UUO group. We evaluated renal TGF-beta mRNA, MCP-1, and osteopontin using real-time RT PCR. We evaluated renal TGF-beta, alpha-SMA, and CD68 by immunohistochemistry. We recorded light microscopic findings of kidney specimens. RESULTS: PC significantly decreased the expression of MCP-1 and alpha-SMA mRNA. Renal gene levels of expression of TGF-beta, MCP-1, and osteopontin in the UUO group were significantly higher than the sham-operated group (p<0.01). The levels of expression of TGF-beta, MCP-1, and osteopontin mRNA of kidneys in the PC-treated UUO group were significantly lower than the untreated UUO group (p< 0.05). The magnitude of expression of TGF-beta and alpha-SMA protein in the kidneys of the PC-treated UUO group was significantly less than the untreated UUO control group (p<0.05). CONCLUSION: The results of the present study suggest that PC has anti-inflammatory and anti-fibrotic effects in an experimental UUO murine model.

Spontaneous Bilateral Renal Rupture in an End-stage Renal Disease Patient Treated with Hemodialysis / 대한신장학회지

Bilateral spontaneous renal rupture is a rare event that has been documented in only a few reports. We report a spontaneous, but not simultaneous rupture of both kidneys in a 64-year-old man with end-stage renal disease who had been treated with hemodialysis for 78 months. He complained of sudden left flank pain. Abdominal computed tomography (CT) revealed a huge perirenal hematoma with multiple renal cysts. The patient underwent an urgent left nephrectomy and was diagnosed as multiple acquired renal cysts with rupture and focal incidental papillary renal cell carcinoma. Twenty-two days after the left nephrectomy, he complained of sudden right flank pain and abdominal CT showed another massive perirenal hematoma. The patient underwent a right nephrectomy and was diagnosed as renal cyst rupture with perirenal hemorrhage. However, there was no evidence of renal cell carcinoma in the right kidney. Postural hypotension and frequent hypotensive episodes developed during hemodialysis several months after both nephrectomies. He was diagnosed as primary adrenal insufficiency with rapid adrenocorticotropic hormone (ACTH) stimulation test and the level of plasma ACTH and was treated with prednisolone and fludrocortisone. The patient died of acute myocardial infarction 32 months after bilateral nephrectomies.

Ankle-Brachial Index and Risk Factors for Peripheral Arterial Disease in Dialysis Patients / 대한신장학회지

PURPOSE: Peripheral arterial disease (PAD) is a predictable marker of coronary heart disease and cerebrovascular disease and its prevalence among chronic kidney disease (CKD) patients especially in end-stage renal disease (ESRD) patients undergoing dialysis is apparently increasing. Ankle-brachial index (ABI) is regarded as an easy, reliable, and noninvasive measure of the presence and severity of lower-extremity PAD (ABI or =0.9) and the prevalence of PAD was analyzed. We measured ABI with VP2000 PWV/ankle-brachial index. We also reviewed the clinical characteristics and evaluated the risk factors of PAD, retrospectively. RESULTS: One hundred seventeen patients on hemodialysis, and twenty one patients on peritoneal dialysis were included in this study. The mean age of total patients was 60.1 (24-84) years old. Thirty five patients out of one hundred thirty eight patients had an ABI index of less than 0.9 (PAD indicative). PAD was independently associated with age (p=0.013), duration of dialysis (p=0.013), history of coronary artery disease and cerebrovascular disease (p=0.001, p=0.001 respectively), diabetes (p=0.034), and increased LDL cholesterol (p=0.004) in univariate analysis. In multivariate logistic regression analysis, duration of dialysis, increased level of LDL-cholesterol and history of coronary artery disease were significantly related with PAD (p=0.008, p=0.019, p=0.018 respectively). CONCLUSION: Duration of dialysis, increased level of LDL-cholesterol and coronary artery disease were independent risk factors for PAD in patients with ESRD on dialysis.

A Case of Spontaneous Subdural Hematoma in a Patient with Autosomal Dominant Polycystic Kidney Disease / 대한신장학회지

Intracranial manifestations associated with autosomal dominant polycystic kidney disease (ADPKD) include arachnoid cysts, dolichoectasias, and subdural hematoma (SDH), although there are only a few reports of SDH in patients with ADPKD. We report a case of spontaneous SDH in a patient with ADPKD. A 33-year-old woman complained of severe nausea and vomiting for 10 days. She had suffered from a headache for several months. She was diagnosed with ADPKD and hypertension 6 years earlier, and the hypertension was well controlled. Her mental state was drowsy in the emergency room. Her blood pressure was 180/105 mmHg. There was no evidence of head trauma. Results of a peripheral blood CBC and blood chemistry analysis were within normal limits, as were the results of a blood coagulation test and urinalysis. She was pregnant and in the eighth week of gestation. Brain magnetic resonance imaging revealed SDH in the left lateral convexity and focally in the right lateral convexity, and brain herniation. Surgical drainage was performed through a burr hole, under general anesthesia. Intra-operatively, 62 mL of liquefied subdural hematoma were removed. She recovered completely without sequelae.

A Case of Lupus-like Glomerulonephritis in an HIV-infected Patient / 감염과화학요법

Many types of glomerulonephritis are associated with human immunodeficiency virus (HIV) infection. We present a case of a 50-year-old Korean man with an HIV infection, who developed nephrotic syndrome and progressive renal failure. Renal biopsy showed lupus-like glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. After the administration of antiretroviral agents and steroids, there was reduction in the amount of proteinuria and improvement in renal function.

A Case of Lupus-like Glomerulonephritis in an HIV-infected Patient / 감염과화학요법

Many types of glomerulonephritis are associated with human immunodeficiency virus (HIV) infection. We present a case of a 50-year-old Korean man with an HIV infection, who developed nephrotic syndrome and progressive renal failure. Renal biopsy showed lupus-like glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. After the administration of antiretroviral agents and steroids, there was reduction in the amount of proteinuria and improvement in renal function.

Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

BACKGROUND/AIMS: Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. METHODS: Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-alpha, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy. RESULTS: Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-alpha, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells. CONCLUSIONS: DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effects.

The Heme Oxygenase-1 Genotype is a Risk Factor to Renal Impairment of IgA Nephropathy at Diagnosis, Which is a Strong Predictor of Mortality

The induction of heme oxygenase-1 (HO-1) ameliorates oxidative stress and inflammatory process, which play important roles in IgA nephropathy. We hypothesized length polymorphism in the promoter region of the HO-1 gene, which is related to the level of gene transcription, is associated with disease severity of IgA nephropathy. The subjects comprised 916 patients with IgA nephropathy and gene data. Renal impairment was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) at diagnosis. The short (S: 28) (GT) repeats in the HO-1 gene was determined. The frequencies of S/S, S/M, M/M, S/L, L/M, and L/L genotypes were 7.2%, 6.9%, 3.1%, 30.8%, 22.7%, and 29.4%, respectively. The baseline characteristics were not different. In the S/S genotypic group, the renal impairment rate was 18.2%, which was lower than 32.2% in the group with M/M, L/M, or L/L genotype. The odds ratio of renal impairment in S/S genotype, compared to that in M/M, L/M, or L/L genotype, was 0.216 (95% confidence interval, 0.060-0.774, p=0.019). The HO-1 gene promoter length polymorphism was related to the renal impairment of IgA nephropathy at diagnosis, which is an important risk factor for mortality in IgA nephropathy patients.

Successful Treatment of Sclerosing Encapsulating Peritonitis with Tamoxifen and Prednisolone / 대한신장학회지

Sclerosing encapsulating peritonitis (SEP) is an uncommon but serious complication of long-term peritoneal dialysis (PD). Entrapment of the intestine in fibrous tissue, causing complete intestinal obstruction, is referred to as SEP. The usual clinical presentation is with partial or complete small bowel obstruction, ascites, abdominal mass, or impaired peritoneal ultrafiltration. Conservative treatment carries a poor outcome and surgery has offered variable results. Even though there is no established medical treatment, immunosuppressive drugs, steroid and tamoxifen are often used. Tamoxifen is a nonsteroidal anti-estrogenic drug commonly used in the management of breast cancer. To our knowledge, this is the first case of sclerosing encapsulating peritonitis successfully treated with tamoxifen and prednisolone in Korea. Recently, we have treated three SEP patients with tamoxifen and prednisolone. All three patients showed clinical improvement within a few months.

The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury / 대한신장학회지

PURPOSE:Preconditioning due to activation of AMPK might reduce ischemia-reperfusion (I/R) injury in the kidney, based on the key role of AMPK in preserving ATP. To evaluate this possibility, the effect of preconditioning with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), AMPK activator, before sustained ischemia was investigated. METHODS:Adult male Sprague-Dawley rats weighing approximately 220-250 g were used. To induce renal ischemia, a laparotomy was performed under ketamine and xylazine hydrochloride, and the blood supply to both kidneys was interrupted by placement of vessel clamps at the level of the renal pedicles. Reflow was initiated by removing the clamps. The following experimental groups were defined 1. Acute renal ischemia 0 sec, 10 min, 15 min, 2. AICAR treatment, 3. Sham group (S), 4. Ischemia/ Reperfusion group (I/R), 5. AICAR+I/R group (A+I/R), 6. AraA (Adenine-9-b-D-arabinofuranoside, an AMPK) inhibitor+AICAR+I/R group (AraA+A+I/R) RESULTS:There was only faint AMPK phosphorylation in the sham group. After 10 minutes of ischemia, or AICAR preconditioning however, Thr172 phosphorylation of AMPK was increased (p<0.05). The serum levels of BUN and creatinine were significantly decreased in AICAR preconditioning group (A+I/R). (128.0+/-7.33 mg/dL, 4.18+/-0.27 mg/dL vs. 90.2+/-11.13 mg/dL, 2.58+/-0.7 mg/dL, p<0.05), but these effects were attenuated by AMPK inhibitor, AraA (AraA+A+I/R group). In quantitative analysis of tubular injury, tubular injury score in AICAR preconditioning group significantly decreased (p<0.05). CONCLUSION:The AMPK activator AICAR has a protective effect against renal I/R injury.

Erythropoietin (EPO) Attenuates Renal Injury in an Experimental Model of Cisplatin-induced Nephrotoxicity in Rats / 대한신장학회지

PURPOSE:In addition to its hematopoietic effects, EPO has protective effects in vivo in several animal models of acute renal injury. We examined whether EPO also attenuated renal injury in a rat model of cisplatin-induced nephrotoxicity via anti-apoptotic and anti-inflammatory actions. METHODS:Male SpragueDawley rats were divided into four groups: control rats, EPO+control rats, cisplatin rats, and EPO+cisplatin rats. EPO treatment was started 24 h prior to cisplatin administration. Then, 96 h after cisplatin administration, all experimental animals were killed. And renal molecular, functional and structural parameters were measured. RESULTS:The serum levels of BUN and creatinine in the 96 h after cisplatin administration were significantly lower than in cisplatin rats. On microscopic examination, the magnitude of renal tubular epithelial damage in the EPO+cisplatin rats was also significantly less than that of cisplatin rats. Renal expression of TNF-alpha Fas, MCP-1 and TGF-betain the cisplatin rats was significantly higher than those of control rats and EPO+control rats. The levels of TNF-alpha Fas, MCP-1 and TGF-betagene expression in EPO+cisplatin rats were significantly lower than those of cisplatin rats. The Bcl-2 mRNA level in EPO+cisplatin rats was significantly higher than in cisplatin rats. EPO+cisplatin rats had significantly fewer TUNEL-positive cells. CONCLUSION:These results suggest that EPO has a protective effect against experimental cisplatin- induced renal injury and that the anti-inflammatory and anti-apoptotic properties of EPO may be involved.