Diagnóstico de nefrosclerosis en fallecidos autopsiados / Diagnosis of nephrosclerosis in autopsied deceased

Introducción: La nefrosclerosis se produce debido al daño de la microvasculatura glomerular. El daño vascular a nivel glomerular, reduce su capacidad funcional y el daño se acelera debido a la hipertensión arterial, diabetes mellitus, obesidad y otros causantes de daño renal. Objetivo: Identificar el diagnóstico histopatológico de nefrosclerosis y describir características de fallecidos autopsiados con esta entidad. Métodos: Fueron analizados 135 449 fallecidos autopsiados en Cuba, de 15 o más años de edad, entre los años 1963 y 2015, se revisaron los diagnósticos histopatológicos de nefrosclerosis. Se precisaron además los diagnósticos de causa directa de muerte y de causa básica de muerte, así como su asociación con otras entidades. Se analizó además: edad, sexo, diagnóstico histopatológico de nefrosclerosis, diagnósticos de causa directa y básica de muerte, y asociación con otras entidades patológicas. Resultados: Hubo diagnóstico histopatológico de nefrosclerosis en 56 422 (40,2 por ciento), de ellos el 91,8 por ciento tenían 55 o más años de edad, el 52,9 por ciento fue del sexo masculino y el 47,0 por ciento femenino. La bronconeumonía (25,88 por ciento) fue la principal causa directa de muerte, los trastornos ateroscleróticos y la hipertensión arterial se identificaron como las principales causas básicas de muerte. Conclusiones: Hubo un elevado porcentaje de diagnósticos de nefrosclerosis en los fallecidos autopsiados en Cuba, en un período de 52 años. Predominaron los pacientes mayores de 55 años, del sexo masculino, así como la asociación con enfermedades básicas ateroscleróticas e hipertensión arterial(AU)

Introduction: Nephrosclerosis occurs due to damage to the glomerular microvasculature. Vascular damage at the glomerular level reduces its functional capacity and the damage is accelerated due to high blood pressure, diabetes mellitus, obesity and other causes of kidney damage. Objective: To identify the histopathological diagnosis of nephrosclerosis and describe characteristics of autopsied deceased with this entity. Methods: 135,449 autopsied deceased in Cuba, aged 15 or over, between 1963 and 2015 were analyzed, the histopathological diagnoses of nephrosclerosis were reviewed. The diagnoses of direct cause of death and basic cause of death were also specified, as well as their association with other entities. It was also analyzed: age, sex, histopathological diagnosis of nephrosclerosis, diagnoses of direct and basic cause of death, and association with other pathological entities. Results: There was a histopathological diagnosis of nephrosclerosis in 56,422 (40.2 percent), of them 91.8 percent were 55 years of age or older, 52.9 percent were male and 47.0 percent female. Bronchopneumonia (25.88 percent) was the main direct cause of death, atherosclerotic disorders and arterial hypertension were identified as the main basic causes of death. Conclusions: There was a high percentage of nephrosclerosis diagnoses in autopsied deceased in Cuba, in a period of 52 years. Male patients over 55 years of age predominated, as well as the association with basic atherosclerotic diseases and arterial hypertension(AU)

Diagnosis and treatment of patients with IgA nephropathy in Japan

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Although CKD is not one specific disease, it is a comprehensive syndrome that includes IgA nephropathy. As reported by the Japanese Society of Nephrology, 13.0 million people have CKD. In Japan, major causes of end-stage kidney disease are type 2 diabetic nephropathy, chronic glomerulonephritis, especially IgA nephropathy, hypertensive nephrosclerosis, and polycystic kidney disease. IgA nephropathy is characterized by polymeric IgA1 with aberrant galactosylation (galactose-deficient IgA1) increased in the blood and deposited in the glomerular mesangial areas, as well as partially in the capillary walls. The tonsils are important as one of the responsible regions in this disease. The clarification of the mechanism of galactose-deficient IgA1 production will pave the way for the development of novel therapies. The results of future research are eagerly awaited. At present, the most important therapeutic goals in patients with IgA nephropathy are the control of hypertension, the decrease of urinary protein excretion, and the inhibition of progression to end-stage kidney disease. Several investigators have reported that renin–angiotensin–aldosterone system inhibitors reduce levels of urinary protein excretion and preserve renal function in patients with IgA nephropathy. In Japan, tonsillectomy and steroid pulse therapy are more effective for patients with IgA nephropathy.

Current characteristics of dialysis therapy in Korea: 2015 registry data focusing on elderly patients

Because of increases in the elderly population and diabetic patients, the proportion of elderly among dialysis patients has rapidly increased during the last decades. The mortality and morbidity of these elderly dialysis patients are obviously much higher than those of young patients, but large analytic studies about elderly dialysis patients' characteristics have rarely been published. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an Internet online registry program and analyzed the characteristics. A survey on elderly dialysis patients showed that more than 50% of elderly (65 years and older) patients had diabetic nephropathy as the cause of end-stage renal disease, and approximately 21% of elderly dialysis patients had hypertensive nephrosclerosis. The proportion of elderly hemodialysis (HD) patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of young (under 65 years) HD patients (69% vs. 80%). Although the vascular access was poor and small surface area dialyzers were used for the elderly HD patients, the dialysis adequacy data of elderly patients were better than those of young patients. The laboratory data of elderly dialysis patients were not very different from those of young patients, but poor nutrition factors were observed in the elderly dialysis patients. Although small surface area dialyzers were used for elderly HD patients, the urea reduction ratio and Kt/V were higher in elderly HD patients than in young patients.

Avaliação laboratorial em pacientes com doença renal crônica submetidos à hemodiálise / Laboratory evaluation in chronic kidney disease patients undergoing hemodialysis

Objetivo: avaliar as alterações nos exames laboratoriais e de capacidade funcional nos pacientes com doença renal crônica (DRC), submetidos à hemodiálise. Métodos: Para a avaliação dos pacientes foram coletados os dados pessoais, histórico de fatores de risco e de comorbidades associadas à DRC, bem como o tempo e a frequência no tratamento hemodilítico, além dos resultados dos exames laboratoriais e da capacidade funcional máxima. Resultados: Dos 23 pacientes estudados, 21,7% apresentavam nefroesclerose como a principal causa de DRC. O sedentarismo apresentou-se como o principal fator de risco. Todos os pacientes apresentaram alteração nos resultados dos exames laboratoriais e de capacidade funcional, sendo que a anemia manifestou-se na totalidade dos pacientes estudados. Observou-se uma associação significativa entre creatinina e ureia. Conclusão: O comprometimento da homeostase corporal, como também da capacidade física em pacientes DRC em homodiálise foi evidenciado.

Thrombotic microangiopathy resulting from neglected blood pressure control

Hypertensive nephrosclerosis is usually associated with chronic hypertension, which increases the risk of progressive renal disease. Among the causes of malignant hypertension, thrombotic microangiopathy is complicated and is associated with renal dysfunction at the time of diagnosis. In this case, a young man with hypertension presented with renal failure and thrombocytopenia in the emergency department. This case emphasizes the importance of early recognition of renal failure and thrombocytopenia among patients with uncontrolled hypertension.

Renal replacement therapy in Korea, 2012

The Korean Society of Nephrology (KSN) launched the official end-stage renal disease (ESRD) patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD) patients, 7,552 peritoneal dialysis (PD) patients, and 14,128 functioning kidney transplant (KT) patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP), and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP). The primary causes of ESRD were diabetic nephropathy (50.6%), hypertensive nephrosclerosis (18.5%), and chronic glomerulonephritis (18.1%). The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively.

Current status of dialysis therapy for ESRD patients in Korea

The Korean Society of Nephrology (KSN) launched the End-Stage Renal Disease (ESRD) Patient Registry in 1985, and the online internet registry program was begun in 2001. The increasing number of elderly people and diabetic patients in Korea has resulted in a very rapid increase in the number of ESRD patients. The total number of dialysis patients was 50,289: 42,596 receiving hemodialysis (HD) and 7,694 receiving peritoneal dialysis (PD) at the end of 2011. The prevalence of dialysis therapy was 972.4 patients per million population (PMP), and the proportion of dialysis therapy was HD: 84.7% and PD: 15.3%. The primary causes of ESRD were diabetic nephropathy (47.1%), hypertensive nephrosclerosis (19.6%), and chronic glomerulonephritis (10.4%). The mean urea reduction ratio of hemodialysis was 68.11% in male HD patients and 74.09% in female HD patients. The mean Kt/V was 1.395 in male patients and 1.660 in female patients. The most common cause of death was cardiac arrest (26%), followed by sepsis (9.7%), cerebro-vascular accident (8.7%), respiratory infection (8.4%), and myocardial infarction (6.6%), respectively. The five-year survival rates of male and female dialysis patients were 65.3% and 68.0% in Korea.

Analysis of ultrastructural glomerular basement membrane lesions and podocytes associated with proteinuria and sclerosis in Osborne-Mendel rats with progressive glomerulonephropathy

The renal glomeruli of 12 male Osborne-Mendel (OM) rats 3 to 24 weeks old were examined by electron microscopy. Effacement of podocyte foot processes (FPs) developed at 3 weeks of age and became progressively worse over time. Loss or dislocation of the slit membrane was also found. Vacuoles and osmiophilic lysosomes appeared in the podocytes starting at 6 weeks of age. Podocyte detachment from the glomerular basement membrane (GBM) was apparent at 18 weeks of age. Laminated GBM was occasionally observed in all animals. These features might lead to the development of spontaneous proteinuria and glomerulosclerosis in OM rats.

Brief Report: Renal replacement therapy in Korea, 2010

The Korean Society of Nephrology (KSN) launched the official End-Stage Renal Disease (ESRD) Patient Registry in 1985 and the Internet online registry program was opened in 2001. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The increasing number of elderly people and diabetic patients in Korea has resulted in a very rapid increase in the number of ESRD patients. The total number of ESRD patients was 58,860 (hemodialysis [HD], 39,509; peritoneal dialysis [PD], 7309; and functioning kidney transplant [KT], 12,042). The prevalence of ESRD was 1144.4 patients per million population (PMP), and the proportion of renal replacement therapy was HD, 67.1%; PD, 12.4%; and KT, 20.5%. The number of new ESRD patients in 2010 was 9335 (HD, 7204; PD, 867; and KT, 1264; the incidence rate was 181.5 PMP). The primary causes of ESRD were diabetic nephropathy (45.2%), hypertensive nephrosclerosis (19.2%), and chronic glomerulonephritis (11.3%). The mean urea reduction ratio was 67.9% in male HD patients and 73.9% in female HD patients. The mean Kt/V was 1.394 in male patients and 1.659 in female patients. Five-year survival rates of male and female dialysis patients were 64.9% and 67.3%, respectively.

Avaliação da perda de função renal no paciente hipertenso e tratamento dessa patologia / Assessment of renal function loss in hypertensive patients and treatment of this pathology

Entre as várias causas primarias de doenças renal em estágio terminal identificadas em pacientes em diálise nos Estados Unidos, podemos identificar a nefropatia diabética como a mais comum, correspondendo a 40%, seguida pela doença vascular, incluindo a nefroesclerose hipertensiva (20%), doença glomerular primária (18%), doença tubulointerstical (7%) e doença cística (5%). A hipertensão está associada à progressão da doença renal de forma mais rápida, independente da causa da base; acrescido a regra de avanço da doença renal, a hipertensão pode ser o fator de risco mais comum aumentando mais vezes o risco de doença cardiovascular observado em pacientes com insuficiência renal. Clinicamente pode-se verificar um ciclo vicioso: “A hipertensão causando lesão renal, a qual aumento os níveis tensionais...”. Esse artigo discorrerá sobre a importância da um seguimento adequado do paciente hipertenso, como diagnosticar a perda de função renal, potencias lesões sobre o órgão, tratamento para cada subtipo de Nefroesclerose e formas de prevenir a perda de função renal no paciente hipertenso.

Intervention of the Dysfunctional and Thrombosed Autogenous Vascular Access / 한양의대학술지

In South Korea at the end of 2006, the total number of patients that had undergone renal replacement therapy was 46,730 (hemodialysis: 62.1%, peritoneal dialysis: 17.1%, functioning kidney transplantation: 20.8%). There were 9,197 new renal replacement therapy patients in 2006 and the incidence rate per million 185.3. In South Korea, the most common primary cause of end stage renal disease was diabetic nephropathy (42.3%), hypertensive nephrosclerosis (16.9%), and chronic glomerulonephritis (13.0%). The National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) has recommended placement of autogenous arteriovenous fistulas over alternatives including the use of arteriovenous grafts and central venous catheters to improve the overall outcome of patients undergoing hemodialysis. However, autogenous arteriovenous fistulas, like polytetrafluoroethylene grafts, are also subject to dysfunction and eventual failure. Since first described in 1982, percutaneous transluminal balloon angioplasty has become the mainstay of treatment for accesses failing because of underlying central or peripheral venous stenoses. When angioplasty alone fails, alternative treatment modalities, including stent placement and atherectomy, allow immediate salvage in most cases. Consequently, interventional treatment should be attempted first for dysfunctional and thrombosed autogenous vascular access and should be initiated in all dialysis centers so long as the local radiologists are trained and enthusiastic.

Valor preditivo do exame de fundo de olho na detecção da nefropatia hipertensiva / Predictive value of the fundoscopy in hypertensive nephropathy

JUSTIFICATIVA E OBJETIVOS: A hipertensão arterial sistêmica (HAS) é conhecidamente uma das principais doenças relacionadas à doença renal crônica. Muitos estudos têm demonstrado uma correlação entre as lesões ateroscleróticas no fundo do olho e o grau de aterosclerose renal, secundário à hipertensão arterial, validando este dado como uma importante rotina semiotécnica para a depuração de nefropatias em hipertensos. O objetivo deste estudo foi verificar a presença de correlação entre esses dois acometimentos. MÉTODO: Foram selecionados 30 pacientes baseados nos critérios de inclusão do estudo. A depuração da creatinina e a microalbuminúria foram utilizadas para avaliar a presença de nefropatia. Alterações retinianas foram estabelecidas pela oftalmoscopia indireta. As correlações foram estudadas pelo método de Spearmam. Análise de múltipla Variância e o teste do Qui-quadrado foram empregados para estabelecer o impacto dos diversos fatores sobre as variáveis. RESULTADOS: 68,2% dos pacientes com retinopatia apresentaram nefropatia hipertensiva (NH), enquanto que 41,7% dos nefropatas tinham também retinopatia hipertensiva (RH) (x2 = 4,75; p < 0,05). Fatores de risco para aterosclerose, fármacos utilizados e os sintomas nefrológicos não diferiram entre os grupos. Pacientes com concomitância de NH e RH, apresentaram valores mais elevados de microalbuminúria quando comparados ao grupo sem acometimento e ao grupo com NH. Detectou-se correlação significativa entre essas complicações (r = 0,42; p < 0,05). CONCLUSÃO: A retinopatia hipertensiva na população estudada, apresentou correlação com a ocorrência da nefropatia hipertensiva. O encontro de alterações microvasculares em pacientes hipertensos, na fundoscopia, sugere investigação da lesão renal.(AU)

BACKGROUND AND OBJECTIVES: Hypertension is a commonly cited cause for declining renal function. Presence of retinal arteriolar abnormalities has been postulated to represent an indicative of systemic microcirculatory damage and renal dysfunction secondary to hypertension. Demonstration of this microvascular damage may provide a useful indicator of at-risk individuals for progressive renal function decline. The purpose of this investigation is to describe the associations between these abnormalities. METHODS: Thirteen patients were recruited based in the inclusion conditions of the study. Glomerular filtration rate and the microalbuminuria were used to evaluate the nephropathy presence. Retinal arteriolar abnormalities were evaluated by using indirect fundoscopy. Correlations were examined by using Spearman correlation test. Test of Multiple Variance and Chi-square test were used to establish the impact of the several factors on the variables. RESULTS: 68.2% of patients with retinopathy showed hypertensive nephropathy (HN), while 41.7% of patients with nephropathy also had hypertensive retinopathy (HR) (x2 = 4.75; p < 0.05). Risk factors for arteriosclerosis, used medications and the nephrological symptoms did not differ among the groups. Cases with both complications (HN + HR), presented higher values of microalbuminuria as comparedto those without HR, with or without HN. Significant correlation was detected between the 2 complications (r = 0.42; p < 0.05). CONCLUSION: This investigation shows correlation between the presence of HR and HN. Presence in the fundoscopy of such retinal microvascular abnormalities, in hypertensive patients, suggests screening for renal dysfunction.(AU)

Alterações renais na hipertensão arterial sistêmica / Renal damage in hypertension

A discussão sobre a interação entre hipertensão arterial e lesão renal vem desde o início so século passado. Dados epidemiológicos atuais apontam a hipertensião arterial sistêmica como o fator de risco mais importante para a perda progressiva da função renal em estudos com pacientes acometidos de doença renal crônica terminal. Existem duas formas distintas de apresentação da lesão renal do paciente hipertenso: a nefroesclerose benigna e a nefroesclerose maligna, sendo ambas distintas tanto do ponto de vista clínico como anatomopatológico. O tratamento da hipertensão arterial visa tanto à prevenção de lesões renais no paciente sem doença prévia como à diminuição da deterioração da lesão renal no paciente com doença renal já instalada, sendo as metas terapêuticas baseadas na redução dos valores da pressão arterial, alvo terapêutico < 130/80 mm Hg, preferencialmente com medicamentos que também diminuam a pressão intraglomerular, como inibidores da enzima de conversão da angiotensina e/ou antagonista da angiotensina II.

Effect of enalapil on renal interstitial fibrosis in rats with unilateral ureteral obstruction / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction(UUO).@*METHODS@#UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly divided into a sham-operated group(n=16), a UUO model group(n=24), and an enalapril treated group(n=24). The rats were treated with 10 mg/kg.d by gastric gavage in the enalapril treated group from 24 h before the operation, and the rats were treated with the identical dose of normal saline in the other 2 groups. The rats were sacrificed at 3,7,14, and 21 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expression of collagen I (Col I) was detected by real-time PCR, and the protein expression of connective tissue growth factor (CTGF) was detected by Western blot.@*RESULTS@#The renal interstitial damage index, relative collagen area and the expression of Col I mRNA and CTGF in the renal tissues in the model group increased with the prolongation of obstruction. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, and inhibted the expression of Col I mRNA and CTGF. There was significant difference on day 3,7,and 14 (P0.05).@*CONCLUSION@#Enalapril significantly attenuates renal interstitial fibrosis by supressing the expression of Col I mRNA and CTGF.

Nefroesclerose hipertensiva / Nefroesclerose hypertensive

Os principais danos causados pela HAS são as lesões em órgãos alvo, como coração, cérebro e rins. A nefroesclerose hipertensiva, é a segunda principal causa de doença renal terminal [DRT]. A nefroesclerose maligna [NM] é conhecida causa de DRT, apresentando elevado custo médico-social, principalmente por sua estreita relação com as doenças cardiovasculares, devendo ser diagnosticada e tratada precocemente.

Renal manifestation in patients with rheumatoid arthritis / 대한내과학회지

BACKGROUND/AIMS: Although renal manifestations are often involved in patients with rheumatoid arthritis (RA), the causal relationship between RA and renal manifestations has not been clearly defined. The prevalence and causes of renal manifestations in patients with RA were investigated in this study. METHODS: The clinical data from 457 patients with RA and who were admitted to Hanyang University Hospital between 2001 and 2005 were retrospectively analyzed. Renal manifestations were defined as proteinuria (> or =300 mg/day) or azotemia (serum creatinine > or =1.7 mg/dL), with or without hematuria. RESULTS: Renal manifestation was present in 82 (17.9%) out of 457 RA patients. Among them, proteinuria was observed in 81 (17.7%), azotemia in 37 (8.1%) and hematuria with either proteinuria or azotemia in 35 (7.7%). For the cases with proteinuria, the amount of preteinuria was 1353+/-207 (mean+/-SD) mg/day. There was no significant correlation between the degree of proteinuria and the duration of RA. For the cases with azotemia, the serum creatinine was 3.98+/-0.35 mg/dL. The presence of azotemia had no significant association with the duration of RA (14.4+/-1.5 vs. 11.6+/-1.2 years, respectively). When the etiology of the renal manifestation was classified into primary and secondary renal disease, the latter included diabetic nephropathy in 13 (15.9%), hypertensive nephrosclerosis in 8 (9.8%), drug induced chronic tubulointerstitial disease in 11 (13.4%) and AA amyloidosis in 2. Renal biopsy revealed 10 cases of primary glomerulopathy, including IgA nephropathy in 3, membranous nephropathy in 2, mesangial proliferative glomerulonephritis in 1, focal segmental glomerulosclerosis in 1 and chronic sclerosing glomerulonephritis in 3. CONCLUSIONS: The prevalence of chronic kidney disease in patients with RA is high, although direct renal invasion by RA is very rarely encountered. Renal biopsy would be of great help to identify the various causes of renal manifestations in patients with RA.

A Case of Polycythemia Vera Combined with Focal Segmental Glomerulosclerosis

Polycythemia vera (PV) is a myeloproliferative disorder that results from clonal expansion of a transformed hematopoietic stem cell, and this is associated with a prominent overproduction of erythrocytes, and to a lesser extent, expansion of the granulocytic and megakaryocytic elements. Secondary polycythemia is occasionally associated with renal diseases such as renal tumors, cysts, hydronephorosis, renal transplantation, renal artery stenosis and Bartter's syndrome, and it is rarely associated with nephritic syndrome, nephrosclerosis, chronic glomerulonephritis (GN) and membranous nephropathy. Although cases of erythrocytosis with concomitant GN have occasionally been reported, there are few reports regarding PV. Focal segmental glomerulosclerosis (FSGS) is one of the most frequent forms of GN. However, its association with PV has rarely been described. We report here on one patient with concomitant PV and FSGS along with a review of the previously reported literature.

A case of minimal change nephrotic syndrome with polycythemia vera / 대한내과학회지

The cause of secondary polycythemia is known to be renal diseases such as renal tumors, renal cysts, hydronephrosis, renal artery stenosis, renal transplantation and Bartter's syndrome. Yet this disease rarely reported in conjunction with nephrotic syndrome, nephrosclerosis, pyelonephritis or chronic glomerulonephritis. There are only rare reports of glomerulonephritis with polycythemia vera. We report here on a case of a minimal change nephrotic syndrome with polycythemia vera. A 60-year-old man visited our hospital due to his elevated hemoglobin level and proteinuria and his elevated neuron specific enolase. The blood hemoglobin level was 22.4 g/dL. The blood level of neuron specific enolase was 36.7 ng/mL. The bone marrow aspirate showed hypercellularity and panmyelosis. Electron microscopy showed diffuse effacement of the epithelial foot processes and microvillous transformation of the foot processes. Treatment was done by performing phlebotomy and administering hydroxyurea. There was decreased urinary protein and normalization of the hemoglobin level following treatment with phlebotomy and hydroxyurea.

Experimental study on effect of Kangxianling on rat renal interstitial fibrosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect and mechanism of Kangxianling (KXL, a TCM herbal compound) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO).</p><p><b>METHODS</b>Eighteen male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KXL group. Renal interstitial fibrosis model was established in rats by UUO. After rats were raised for additional 14 days, their body weight, serum levels of creatinine (SCr) and blood urea nitrogen (BUN) were analyzed. Then rats were sacrificed, their renal pathology examined by HE staining and PASM staining; expressions of transforming growth factor-beta1 (TGF-beta1), hepatocyte growth factor (HGF) mRNA, and a-smooth muscle actin (alpha-SMA), TGF-beta1 receptor I (TbetaR I), TGF-beta1 receptor II (TbetaR II) and hepatocyte growth factor receptor (C-Met) protein in kidney tissue were determined by RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>SCr and BUN in the model group were significantly higher than those in the sham operated group (P <0.05). Expressions of TGF-beta1 mRNA and a-SMA, TbetaR I , TbetaR II and C-Met protein in kidney tissue in the model group significantly up-regulated and mRNA expression of HGF significantly down-regulated, and obvious hyperplasia of the base member of glomeruli was seen. After intervention with KXL, BUN content significantly lowered, alpha-SMA, TbetaR I and TbetaR II protein expression decreased and HGF mRNA expression up-regulated significantly in the treated group, with slight pathological changes only shown as mild hyperplasia of the base member of glomeruli and renal tubules.</p><p><b>CONCLUSION</b>KXL could inhibit the protein expressions of a-SMA, TbetaR I , TbetaR II and increase the mRNA expression of HGF, which is a protective factor against renal fibrosis. Therefore, it is effective in alleviating the renal interstitial fibrosis and improving the renal function in UUO rats.</p>

Two Cases of Isolated Diffuse Mesangial Sclerosis with WT1 Mutations

Here we report two cases of isolated diffuse mesangial sclerosis (IDMS) with early onset end-stage renal failure. These female patients did not show abnormalities of the gonads or external genitalia. Direct sequencing of WT1 PCR products from genomic DNA identified WT1 mutations in exons 8 (366 Arg>His) and 9 (396 Asp>Tyr). These mutations have been reported previously in association with Denys-Drash syndrome (DDS) with early onset renal failure. Therefore we suggest that, at least in part, IDMS is a variant of DDS and that investigations for the WT1 mutations should be performed in IDMS patients. In cases with identified WT1 mutations, the same attention to tumor development should be required as in DDS patients, and karyotyping and serial abdominal ultrasonograms to evaluate the gonads and kidney are warranted.