Serpin-A3 is Associated with Persistent Albuminuria in Adolescents with Secondary Podocytopathy, in a Region with High Prevalence of Chronic Kidney Disease of Unknown Origin

Abstract Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete podocyte fusion, probably associated with oligonephrony. To date, urinary biomarkers have not been explored in this population. Objective: The aim of the study was to identify the presence of potential biomarkers of early renal injury in patients with pA (pACR) and that correspond with the characteristic nephropathy profile that prevails in this entity. Methods: This is a cross-sectional, analytical, and comparative study. Four groups were recruited: adolescents aged 10-17 years with pACR, isolated albuminuria (iACR), no albuminuria (negative control), and adults with biopsy-confirmed glomerulopathy (positive control). Urinary excretion of SerpinA3, heat-shock protein-72 (HSP-72), podocalyxin (PCX), and nephrin was evaluated in urine samples. SerpinA3 and HSP-72 were analyzed by Western blot, and PCX and nephrin were quantified by enzyme-linked immunosorbent assay. Results: The mean GFR in the pACR group was 113.4 mL/min/1.73m2 and differed significantly only from that of the positive control group (65.1 mL/min/1.73m2). The mean albuminuria value in the pACR group was 48.9 mg/g. SerpinA3 concentration differed between groups (0.08 vs. 0.25 ng/mL, p < 0.001): it was significantly higher in the pACR group compared to the negative controls (p = 0.037). Conclusion: SerpinA3 was significantly associated with pA and could become a biomarker of early kidney injury. Further investigations are required to determine whether SerpinA3 precedes the development of albuminuria and its pathogenic role.

Renal Protective Effect of Bupi Yishen Decoction on Diabetic Kidney Disease Rats Based on Tubuloglomerular Feedback / 中国实验方剂学杂志

ObjectiveTo observe the influence of Bupi Yishen decoction on the curative effect of diabetic kidney disease rats and the tubuloglomerular feedback. MethodAmong the 100 SD male rats， 25 were randomly selected as the normal group， and the remaining 75 were treated with high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin （STZ） to establish diabetic rat model. The model rats were randomly divided into model group， Bupi Yishen group and losartan group. Bupi Yishen group and Losartan group were given Bupi Yishen decoction （23.4 g·kg-1） and losartan tablet （9 mg·kg-1）， respectively by gavage， and normal group and model group received equal volume of distilled water via intragastric administration. The treatment lasted for 11 consecutive weeks. Random blood glucose was measured once every two weeks. Rats in each group were put into metabolic cage and 24-hour urine volume was recorded. At the end of week 11， the rats were sacrificed for index detection. Enzyme linked immunosorbent assay （ELISA） was used to determine the quantification of 24-hour urinary microalbumin excretion rate （24 h UAER）， renal tubular injury-related proteins and urine creatinine. Blood was collected for creatinine and urea nitrogen detection. Hematoxylin-eosin （HE） staining， periodic acid-schiff （PAS） staining and Masson staining were performed to observe the pathological changes of the kidney of rats. The expression of sodium-glucose cotransporter 1 （SGLT1）， sodium-glucose cotransporter 2 （SGLT2）， sodium-potassium-chloride cotransporter 2 （NKCC2） and connexin 40 （CX40） was detected by immunohistochemistry. The location of adenosine type Ⅰ receptor （A1AR） in kidney was observed by immunofluorescence. In addition， the expression of SGLT1， SGLT2， NKCC2， CX40 and A1AR in renal tissues was determined by Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， renal pathology in model group showed increased glomerular volume， thickened basement membrane， and shed renal tubule epithelial cells. Compared with the model group， the renal pathology of bupiyishen group was improved. Compared with normal group， random blood glucose at different time points， 24 h UAER and renal tubule-injury-related proteins were increased in model group （P<0.01）， and the expressions of SGLT1 and SGLT2 in renal tissue were increased （P<0.01）， and the expression of NKCC2， CX40 and A1AR decreased （P<0.01）. Compared with the model group， the random blood glucose， 24 h UAER and renal tubular injury-related proteins in Bupi Yishen group decreased （P<0.01）， the expressions of SGLT1 and SGLT2 were down-regulated， and the expressions of NKCC2， CX40 and A1AR were increased （P<0.05）. ConclusionBupi Yishen decoction can improve glomerular and renal tubular injury and alleviate early hyperfiltration in diabetic kidney disease rats. The intervention effect of Bupi Yishen decoction on diabetic kidney disease is related to the regulation of tubuloglomerular feedback.

Sub-morbid dehydration-associated glomerular hyperfiltration: An emerging reality?

BACKGROUND: Severe dehydration decreases renal perfusion. However, it is unclear whether sub-morbid dehydration affects kidney function similarly. Although there have been numerous animal and human studies that have suggested mild dehydration is associated with glomerular hyperfiltration, it has not been confirmed on a large-scale in the general population. Therefore, we aimed to identify the relationship between hydration status and kidney function. METHODS: We reviewed the data of 28,342 adults who participated in the Korea National Health and Nutrition Examination Surveys. Urine specific gravity unit (SGU) was the primary variable that indicated hydration status, and the estimated glomerular filtration rate (eGFR) was used as the primary outcome. RESULTS: Multivariate linear regression analysis showed urine SGU was positively associated with eGFR, which was J-shaped in the multivariate generalized additive model plot. In the penalized spline curve analysis, the odds ratio for high eGFR was steadily increased. Although increased urine SGU was associated with decreased blood pressure and pulse rate, it had no effect on increased fasting glucose and total cholesterol, suggesting conflicting cardio-metabolic dehydration effects. CONCLUSION: Dehydration, presumably sub-morbid in an ambulatory community-dwelling general population, is associated with higher kidney function. The clinical significance of sub-morbid dehydration-associated glomerular hyperfiltration needs further investigation.

iSGLT2 y su potencial efecto nefroprotector en pacientes con diabetes mellitus 2 / iSGLT2 and its potential nephroprotector effect in patients with diabetes mellitus 2

Resumen: La diabetes mellitus 2 es una epidemia mundial, aunado a esto, la nefropatía diabética se ha convertido en la principal causa de insuficiencia renal en etapa terminal. En los pacientes con diabetes mellitus 2 existe sobreexpresión de los cotransportadores de glucosa ligados a la vía del sodio tipo 2 (SGLT2) que contribuyen al mantenimiento de la hiperglucemia. Por tanto, los inhibidores de este transportador representan un tratamiento innovador independiente de la acción de la insulina o la función de las células beta pancreáticas. En estudios recientes se ha demostrado que los iSGLT2 tienen efectos benéficos en la microvasculatura, en especial en la progresión de la nefropatía diabética. Este efecto no sólo se debe a la mejora del control glucémico, sino también a efectos directos en el riñón. Los iSGLT2, al inducir la glucosuria, revierten la glucotoxicidad renal. En estudios experimentales se ha observado que, además, se reduce la hiperfiltración, así como los marcadores inflamatorios y fibróticos. También se ha visto reducción del volumen circulante efectivo y aumento en la actividad de bloqueadores del sistema renina-angiotensina-aldosterona (bloqueadores RAA) circulantes, creando así un efecto nefroprotector.

Abstract: Type 2 diabetes mellitus 2 (DM2) is already a worldwide epidemic, in addition, diabetic nephropathy has become the leading cause of end-stage renal failure. In patients with DM2 there is an increased expression of the sodium-glucose cotransporters 2 (SGLT2) that contribute to the maintenance of hyperglycemia. Therefore, the inhibitors of this transporter represent an innovative therapy independent of the action of insulin or the function of pancreatic beta cells. Recent studies have shown that iSGLT2 have beneficial effects on microvasculature, especially in the progression of diabetic nephropathy. This effect is due not only to improved glycemic control but also to direct effects on the kidney. iSGLT2 induce glycosuria to reverse renal glucotoxicity. In experimental studies it has been observed that, in addition, hyper-filtration as well as inflammatory and fibrotic markers are reduced. There has also been a reduction in effective circulating volume and an increase in the activity of circulating renin-angiotensin-aldosterone system blockers (RAA blockers), thus creating a nephroprotective effect.

Salvianolic acid A ameliorates AGEs-induced glomerular endothelial dysfunction and protects against diabetic nephropathy / 中国药理学与毒理学杂志

OBJECTIVE Diabetic nephropathy (DN) has been one of the most common complications of diabetes and the leading cause of end-stage renal disease. Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities. Salvi?anolic acid A (SalA) has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy. The present study was designed to investigate the effects of SalAon glomerular endothelial dysfunctionand diabetic nephropathy. METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products (AGEs). AGEs-induced changes of RhoA/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunoflu?orescence. The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin (35 mg·kg- 1, ip). Renal function and architectonic changes were evaluated by biochemical assay and PAS staining. RESULTS SalA 3μMameliorated AGEs- induced glomerular endothelial permeability (P<0.05) and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-RhoA/ROCK pathway. SalA 1 mg · kg- 1 markedly reduced endothelium loss (P<0.01) and glomerular hyperfiltration (P<0.05) in diabetic kidney. Subsequently,SalA 1 mg·kg-1 suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen (BUN), serum creatinine (Scr) and serum n-acetyl-β-d-glucosaminidase (NAG). AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg-1. CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability, and effec?tively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway. Thus, SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

The Possible Mechanisms through Which Dietary Protein Increases Renal Blood Flow and Glomerular Filtration Rate.

Obesity has been associated with a multitude of co-morbid conditions, most importantly with diabetes mellitus and cardiovascular diseases. Diet is one of the major key factors of a successful weight management schemes to ensure a healthy weight. High protein, low carbohydrate and low fat diets are reported to be effective for weight management and gained particular popularity in the recent past. As a result, most individuals have shifted to high protein diet in an attempt to lose weight or maintain a healthy weight or body composition. On the other hand, high dietary protein is well known to increase renal blood flow and glomerular filtration rate and may potentially increase the future risk of renal disease due to increased glomerular pressure and hyperfiltration injury. The mechanism by which protein diet acts on the kidney is not well known; however, multiple potential mechanisms have been postulated. This review discusses the possible mechanisms through which dietary protein intake may influence renal function parameters.

Patofisiología de la hiperfiltración glomerular en la diabetes. Parte II / Pathophysiology of glomerular hyperfiltration in diabetes. Part II

La hiperfiltración glomerular (HF) en la enfermedad renal diabética es un complejo fenómeno hemodinámico que ocurre en etapas tempranas de la evolución de la enfermedad, y muy probablemente tenga influencias negativas, en cuanto a la progresión hacia la aparición de la microalbuminuria y la evolución de la nefropatía diabética (NFDBT) evidente. Los factores involucrados en su fisiopatología son múltiples, e incluyen al medio diabético y numerosos factores humorales como óxido nítrico, prostaglandinas, sistema renina angiotensina aldosterona, péptido auricular natriurético, especies reactivas de oxígeno y otros factores humorales y de crecimiento, que actúan básicamente provocando o potenciando la vasodilatación de la arteriola aferente (AA)...

Glomerular hyperfiltration (GH) in diabetic renal disease is a complex hemodynamic phenomenon that occurs early in the course of the disease and most likely has associated with poor prognosis with respect to the development of microalbuminuria and overt diabetic nephropathy. The factors involved in its pathophysiology are multiple and include the diabetic milieu and the effects of several humoral factors such as nitric oxide, prostaglandins, renin angiotensin aldosterone system, atrial natriuretic peptide, reactive oxygen species and other humoral and growth factors that act basically causing or enhancing the afferent arteriole vasodilation (AA)...

Fisiopatología de la hiperfiltración glomerular en la diabetes. Parte I / Pathophysiology of glomerular hyperfiltration in diabetes. Part I

La hiperfiltración (HF) glomerular en la enfermedad renal diabética es un complejo fenómeno hemodinámico que ocurre en etapas tempranas de la evolución de la enfermedad, y muy probablemente tenga influencias negativas, en cuanto a la progresión hacia la aparición de la microalbuminuria y la evolución de la nefropatía diabética (NFDBT) evidente. Los factores involucrados en su fisiopatología son múltiples, e incluyen al medio diabético y numerosos factores humorales como óxido nítrico, prostaglandinas, sistema renina angiotensina aldosterona, péptido auricular natriurético, especies reactivas de oxígeno y otros factores humorales y de crecimiento, que actúan básicamente provocando o potenciando la vasodilatación de la arteriola aferente (AA), o factores con propiedad de vasoconstricción de la arteriola eferente, todos considerados como factores vasculares primarios. No obstante, estos factores no pueden explicar otras alteraciones observadas y que componen anormalidades tubulares primarias, como la mayor reabsorción en el túbulo contorneado proximal, probablemente condicionada por el crecimiento renal en la DBT y por la sobreexpresión del cotransportador SGLT2. Esta mayor reabsorción proximal generaría una menor llegada de solutos a la mácula densa (MD), lo cual sería incompatible con una acción del sistema de balance glomérulo tubular, pero sí con una acción mediada por el feedback túbuloglomerular (FBTG) que sensaría esta disminución de la concentración de ClNa en la MD, desactivando el FBTG y produciendo vasodilatación de la AA, con el consiguiente aumento del filtrado glomerular (FG) y del flujo plasmático renal (FPR), característicos del proceso de HF. Estos dos procesos (vascular y tubular) podrían actuar en forma sinérgica o simultánea, dependiendo de las condiciones metabólicas y evolutivas de la enfermedad renal diabética. Similares mecanismos podrían explicar la paradoja de la sal, por la cual una dieta baja en sal exacerbaría el fenómeno de HF, y una dieta alta en sal disminuiría el FG y el FPR, lo cual podría tener iA las medidas terapéuticas habituales del control metabólico estricto, la dieta hipoproteica y el uso de IECA o bloqueantes AT1, no testeados clínicamente para este fin, pero de extendido uso clínico, parecen agregarse los nuevos inhibidores específicos del cotransportador SGLT2, que han demostrado efectos beneficiosos en varios aspectos del manejo de los diabéticos y ya existen algunos trabajos con efecto específico sobre la HF que parecen ser alentadores. Menos experiencia existe con el uso potencial del péptido C, como herramienta terapéutica en estas situaciones clínicas. Es evidente que determinar con más claridad los mecanismos involucrados en este complejo fenómeno, permitirá un mejor conocimiento del mismo y un mejor abordaje terapéutico.mplicancias clínicas inesperadas.

Glomerular hyperfiltration (HF) in diabetic kidney disease is a complex hemodynamic phenomenon which occurs in early stages of the disease'Ts progress and probably has negative influences, regarding the progression to the occurrence of microalbuminuria and the progress of evident diabetic nephropathy (DN). Factors involved in its physiopathology are numerous, they include: diabetic biochemical environment and several humoral factors like nitric oxide, prostaglandins, renin-angiotensin-aldosterone system, atrial natriuretic peptide, reactive oxygen species, other humoral and growth factors. These factors cause or enhance the vasodilatation of the afferent arteriole (AA). Factors with vasoconstriction function over the efferent arteriole, all considered primary vascular factors. However, these factors cannot explain other observed alterations and they constitute primary tubular abnormalities such as the increased reabsorption at the proximal tubule, probably conditioned by kidney growth in DBT and by the overexpression of the SGLT2 cotransporter. This higher proximal reabsorption would produce a lower arrival of solutes to the macula densa (MD). This would be incompatible with an action of the tubuloglomerular balance system, but it would be compatible with an action performed by the tubuloglomerular feedback system (TGFB) that senses the decrease of the ClNa concentration at the MD. Also deactivating the TGFB and causing vasodilatation of the AA, resulting in an increase of glomerular filtration (GF) and renal plasma flow (RPF), characteristic of the HF process. These two processes (vascular and tubular) could act in synergy or simultaneously, depending on the metabolic and progressing conditions of the diabetic kidney disease. Similar mechanisms could explain the salt paradox, whereby a lowsalt diet would exacerbate the HF phenomenon and a high-salt diet would decrease the GF and the RPF, which could result in unexpected clinical implications. The common therapy measures for HF strict metabolic control, a low-protein diet, and the wide clinical use of IECA or AT1 blockers (not clinically tested for this purpose) seem to be added to the new specific inhibitors of the SGLT2 cotransporter, which have shown beneficial effects in several aspects of the diabetic management. There are already some works with specific effect over the HF that seem to be encouraging. There is less experience with the potential use of C-peptide, as a therapeutic tool in these clinical situations. Clearly, defining the mechanisms involved in this complex phenomenon, will allow a better knowledge of it and a better therapeutic approach.

Multicystic Dysplastic Kidney: A Retrospective Study.

Objective: To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. Methods: Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. Results: Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. Conclusion: Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys.

Comprehensive approach to diabetic nephropathy

Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin-angiotensin-aldosterone system inhibitors (RAASi). The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.

The Usefulness of External Bandage Suture for Management of Bleb after Trabeculectomy with Mitomycin C

PURPOSE: To evaluate the usefulness of external bandage suture for bleb-related management that follows trabeculectomy with mitomycin C. METHODS: External bandage sutures were performed on 10 patients having hypotony maculopathy, persistent low intraocular pressure (IOP) caused by either hyperfiltration or focal leakage, or a persisting large bleb caused by hyperfiltration and who received trabeculectomy using mitomycin C as an adjuvant treatment. The changes in IOP measured before and 4 weeks after the procedure along with complication incidences were evaluated. RESULTS: The mean IOP 4 weeks after the procedure compared with the mean IOP prior to the procedure increased from 5.8 +/- 2.0 mm Hg (3.0-9.0 mm Hg) to 14.1 +/- 8.5 mm Hg (4.0-32.0 mm Hg), with statistical significance (p = 0.008). After the procedure, improvement in visual acuity was observed but without statistical significance. One patient had persistent focal leakage from an avascular bleb and conjunctival advancement with removal of the avascular conjunctiva was performed. CONCLUSIONS: An external bandage suture can be a good alternative for correction of post-trabeculectomy hypotony and severe chemosis with minimal effect on blebs while correcting focal leakage and hyperfiltration.

Rol del sistema kallicreína kinina y su interrelación con sistemas vasoactivos durante la preñez / Role of the kallikrein kinin system and its interrelationship with vasoactive systems in pregnancy

La hiperfiltración glomerular y el aumento de la reabsorción de sodio son factores fundamentales para el desarrollo de la unidad feto placentaria. Dichos factores resultan de adaptaciones hemodinámicas y renales en las que participan sistemas vasoactivos. Se pudo demostrar en ratas que la activación del sistema kallicreína kinina (SKK) precede a la instalación de la hiperfiltración glomerular, dado que su inhibición por aprotinina previene el aumento del filtrado glomerular. Además, la inhibición individual o asociada de los efectores específicos del SKK, las prostaglandinas (PGs) y el óxido nítrico (ON), confirman la dependencia del filtrado glomerular del SKK durante la preñez. Encontramos también que el sistema renina angiotensina (SRA) participa en la generación de la hiperfiltración glomerular dado que ésta es afectada por la administración de bloqueantes del SRA. La inhibición máxima sobre el pico de hiperfiltración se obtuvo con el bloqueo de ambos sistemas (SKK y SRA). Además, estrategias para alterar la hiperfiltración glomerular y la reabsorción de sodio de la preñez evidenciaron alteraciones en el desarrollo de la unidad feto placentaria, menor número de crías, mayor cantidad de reabsorciones intrauterinas y retardo en el crecimiento. El tratamiento combinado de inhibidores del SKK asociados a bloqueantes del SRA o de óxido nítrico mostraron los mayores efectos. En consecuencia, demostramos que el SKK juega un rol central en los fenómenos de adaptación que acompañan la preñez normal. La interrelación del SKK con varios sistemas vasoactivos parecería formar una red que participa en las adaptaciones hemodinámicas para un adecuado desarrollo de la gestación y de la unidad feto-placentaria.

Glomerular hyperfiltration and increased sodium reabsorption are key factors for the development of the fetus and placenta in pregnancy. These adjustments result from hemodynamic and renal factors involving vasoactive systems. It was demonstrated in rats that activation of KKS precedes the installation of glomerular hyperfiltration as aprotinin prevents the increase in glomerular filtration. In addition, individual or associated inhibition of specific kallikrein kinin system effectors, prostaglandins (PGs) and nitric oxide (NO), confirm the glomerular filtration rate dependence of KKS during pregnancy. It was also found that the renin-angiotensin system (RAS) contributes to glomerular hyperfiltration as this is affected by the administration of RAS blockers. The peak of hyperfiltration maximum inhibition was obtained by the blockade of both systems (KKS and RAS). In addition, strategies used to alter the glomerular hyperfiltration and increased sodium reabsorption during pregnancy, showed abnormalities in the development of the fetus and placenta, fewer offspring, more fetus resorptions and intrauterine growth retardation. KKS inhibitors associated with RAS or nitric oxide blockers showed the greatest impact. As a consequence, it was demonstrated that KKS plays a central role in the adaptation phenomenom that accompanies normal pregnancy. The interplay of KKS with several vasoactive systems, seem to arrange a network involved in the hemodynamic adaptations to allow the proper development of pregnancy and the fetus and placenta.

Alteraciones renales en la drepanocitosis / Renal disorders in sickle cell disease

La drepanocitosis está asociada con un amplio espectro de alteraciones renales que tienen su base en la falciformación de los eritrocitos en los vasos de la médula renal, que conduce a fenómenos de isquemia, microinfartos y anomalías de la función tubular. Se producen también alteraciones glomerulares funcionales reversibles de la autorregulación renal (hiperfiltración), que pueden conducir a cambios anatómicos irreversibles con glomeruloesclerosis segmentaria focal. Estas anomalías se expresan tempranamente como microalbuminuria, proteinuria y de forma mas tardía, como síndrome nefrótico e insuficiencia renal crónica. Medidas terapéuticas como el uso de inhibidores de la enzima convertidora de la angiotensina II, de los bloqueadores del receptor de la angiotensina II, asociados o no con la hidroxiurea, pueden prevenir o retardar el daño glomerular. En el presente trabajo se exponen de forma resumida aspectos relacionados con la fisiopatología del daño renal en la drepanocitosis y su tratamiento

Sickle cell disease is associated with a wide range of renal disorders resulting from the falciformation of erythrocytes in vessels of the renal medulla, leading to ischemia, microinfarctions and tubular function abnormalities. Reversible glomerular functional renal self-regulation disorders (hyperfiltration) also occur, which may lead to irreversible anatomical changes with focal segmental glomerular sclerosis. These anomalies are expressed at an early stage as microalbuminuria and proteinuria, and at a later stage as nephrotic syndrome and chronic renal failure. Therapeutic measures such as the use of angiotensin-II converting enzyme inhibitors and angiotensin-II receptor blockers, associated or not with hydroxyurea, may either prevent or delay glomerular damage. The paper succinctly presents the physiopathology of renal damage in drepanocytosis and its treatment

Função renal e proteinúria antes e após a doação de rim / Renal function and proteinuria before and after kidney donation

Introdução: Em estudos clínicos, doação de rim para transplante intervivos foi considerada como um procedimento com riscos mínimos a longo prazo paraos doadores, mas os efeitos da redução de massa renal não estão ainda bem definidos. Curiosamente, vários estudos publicados comparam o clearancede creatinina (ClCr) e proteína urinária excretada (PUE) obtidos em doadores antes (dois rins) e após (um rim) a nefrectomia sem considerar os valoresrelativos a um único rim. Metodologia: Nós comparamos a ClCr e PUE, antes e depois da nefrectomia em 21 doadores. Definimos que as metades dosvalores do ClCr e PUE obtidos antes da nefrectomia foram consideradas os valores presumíveis de cada rim, ClCr/2 e PUE/2, respectivamente. O ClCr foicalculado usando a fórmula de Cockcroft-Gault e a PUE foi medida usando urina coletada em 24 horas antes e depois de doação de rim. Resultados: Osresultados demonstram que o ClCr/2 aumentou de 51 ± 2,4 para 78 ± 3,8 ml/min por rim (p <0,0001), e a PUE/2 aumentou de 34,0 ± 3,5 para 205,4 ± 34,0mg/24hs por rim (p <0,0001). Conclusão: Nós concluímos que a hiperfiltração está presente no rim remanescente após a doação. Após a nefrectomia ototal de proteína excretada ainda permanece dentro dos valores considerados normais, mas é importante notar que esta excreção é feita agora através desomente um rim e representa um aumento aproximado de seis vezes dos valores iniciais.

Introduction: In clinical studies, kidney donation for living-related allograft transplantation has been reported as a procedure with minimal long-term risk forthe donors, but the effects of reduced renal mass have not been defined yet. Curiously, many clinical published studies compare creatinine clearence (CrCl)an urinary protein excretion (UPE) obtained in donors before (two kidneys) and after (one kidney) nephrectomy without concerning to the values for eachone kidney. Method: We compared the CrCl and UPE, before and after nephrectomy in 21 donors. We the half of the values for CrCl and UPE obtainedbefore nephrectomy as the presumable initial value for each kidney (CrCl/2 and UPE/2, respectively). The CrCl was estimated by using Cockcroft-Gaultformula and the UPE was measured using urine collected in 24 hours before and after kidney donation. Results: Our results demonstrated that CrCl/2increased from 51 ± 2.4 to 78 ± 3.8 ml/min per kidney (p<0.0001), and the UPE/2 increased from 34.0 ± 3.5 to 205.4 ± 34.0 mg/24hs per kidney (p<0.0001).Conclusion: We conclude that hyperfiltration in the remaining kidney is present after donation and is associated with a considerable increase in the UPEby each kidney. After nephrectomy, the total amount of protein excreted is in the normal range but what calls the attention is the fact that it represents asix-fold increase in protein excretion for the remnant kidney.

Impacts of Metabolic Demand and Renal Mass Supply on the Early Graft Function Following Living Donor Renal Transplantation / 대한이식학회지

PURPOSE: Chronic rejection accounts for the majority of late renal graft losses and there is good evidence that both immunologic and non-immunologic factors are important in late graft loss. The hyperfiltration hypothesis postulates that kidneys with reduced renal mass will progress toward failure due to hypertrophy of the remaining nephron to meet the excess metabolic demand, eventually leading to nephron exhaustion. The impact of metabolic demand and renal mass supply on the early graft function, especially hyperfiltration phenomenon, remains uncertain. METHODS: In this study, we analyzed age, gender, body weight, height, body surface area (BSA), lean body weight (LBW), and serum creatinine (SCr) of both donors and recipients. We weighed the donated kidney and measured the recipient's SCr and LBW for six months postoperatively. Modified Cockcroft-Gault Equation standardized for BSA was used to calculate renal glomerular filtration rate (CrCl, mL/min/1.73 m2). The variables and the CrCl of the 3rd day and 6th month were analyzed with accordance to donor/recipient LBW ratio(D/R LBW) and graft weight/recipient LBW (GW/RLBW) by independent sample t-test and paired t-test using SPSS, and P1), the 3rd day and 6th month CrCl were 80.82+/-28.74 and 71.66+/-12.12, respectively. In R group (D/R LBW3), the 3rd day CrCl was 86.08+/-25.13, which was significantly decreased to 73.48+/-11.64 at the 6th month (P=0.023). In L group (GW/RLBW< or =3), the 3rd day and 6th month CrCl were 66.95+/-19.94 and 73.34+/-10.60 (P=0.158), respectively. the 3rd day CrCl of H group was higher than that of L group significantly (P=0.047), but 6th month CrCl showed no difference between the two groups (P=0.975). CONCLUSIONS: The 3rd day CrCl represents early graft function well. GW/RLBW has a strong correlation with early graft function. In L group with low early graft function, CrCl was tended to be increased to meet the metabolic demand for following the 6 months. Conversely, in H group with high early graft function, CrCl was decreased to reduce the excess graft function. So the 6th month CrCl represents adapted graft function. In this study, therefore, we postulate that the hyperfiltration or hypofiltration develops according to metabolic demand and renal mass supply.

Surgical Outcomes of Conventional Trabeculectomy Converted from Deep Sclerectomy with Collagen Implant (DSCI)

PURPOSE: To assess the surgical outcomes of the conventional trabeculectomy converted from DSCI due to a perforation of trabeculo-descemet's membrane during surgery. METHODS: We retrospectively analyzed the surgical outcomes of 9 patients (11 eyes) who underwent the conventional trabeculectomy converted from DSCI during surgery. RESULTS: The mean age of the subjects was 44.6+/-17.8 years. The types of glaucoma of the subjects were primary open angle glaucoma in nine eyes and secondary glaucoma in two eyes. The mean preoperative intraocular pressure(IOP) was 23.4+/-9.5mmHg with 3.0+/-1.2 of mean anti-glaucoma medications. The mean immediate postoperative IOP was 7.7+/-5.3mmHg and 10.5+/-3.9 mmHg with 0.5+/-0.5 of mean anti-glaucoma medications after 12.0+/-6.6 months of mean follow-up period. Defining the qualified success to be 6 to 21 mmHg of IOP with 2 or lower glaucoma medication without complications such as hypotony maculopathy, the success rate was 82%. There were four eyes (36%) having IOP below 4 mmHg and shallow anterior chamber at one day postoperatively. Two eyes of them recovered within 2 weeks, but the other two (18%) developed hypotony maculopathy. Cataract progressed in two eyes (18%). CONCLUSIONS: The surgical outcomes of conventional trabeculectomy converted from DSCI during surgery was comparable to the elective trabeculectomy, but there was a tendency to have more complications associated with hyperfiltration at the immediate postoperative period.

Role of nitric oxide in the pathogenesis of diabetic nephropathy in streptozotocin-induced diabetic rats

OBJECTIVES: Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. METHODS: To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. RESULTS: Diabetic rats exhibited significantly elevated plasma and urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. CONCLUSIONS: NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest that excessive NO production may contribute to renal hyperfiltration and hyperperfusion in early diabetes.

Hyperfiltration Affecting the Outcome of Living-related Renal Allograft / 대한신장학회잡지

It is well known that immunologic factors like rejection episode and HLA missmatch influence allograft loss and prognosis. However, non-immu- nologic factors such as glomerular hyperfiltration may also have an effect on the survival of the allograft. We measured relative kidney function(dkRF) by DMSA scan, GFR(dGFR) using EDTA and CCr dCCr) by 24-hour urine collection in donors of 70 adult living-related renal allografts engrafted at a single center between December 1992 and January 1994 as a donor work-up before transplantation, and calculated donated kidney GFR(dkGFR=dGFRxdkRF) and CCr(dkCCr=dkCCrxdkRF). We observed graft function for 5 years and analyzed the prognostic factors for the graft. Graft dysfunction was defined as the increase of serum creatinine 5 years after transplantation more than 1.5 times of stabilized serum creatinine at 3 months after transplantation. 1) Sixty patients were followed up for 5 years. Graft dysfunction was observed in 22 patients(37%) and maintenance renal replacement therapy was required in 9(15%) of them. 2) Of the non-immunologic factors, donor age was older in patients with graft dysfunction(51 +/- 12 years) than those without it(34 +/- 11 years, p<0.01), but dkGFR(54.1 +/- 12.2ml/min vs. 58.5 +/- 11.9mVmin), dkCCr(44.8 +/- 14.3mVmin vs. 50.74 13.4ml/min) and the ratio of body surface area(recipient/donor, 0.964 0.14 vs. 0.990.12) were not different in the two groups. Age of recipients and occurrence of graft glomerulopathy also were not different in the two groups. The episode of acute rejection was more frequent in patients with graft dysfunction(32%, 7/ 22) than those without it(3%, 1/38, p<0.01), but the degree of HLA missmatch was not different. In multivariate analysis, donor age(p<0.01) and the episode of acute rejection(p<0.05) were independent factors affecting graft dysfunction. 3) Donor age was older(52 +/- 12 vs. 3814 years, p<0.01) and the episode of acute rejection was more frequent(56%, 5/9 vs. 696, 3/51, p<0.01) in 9 patients with graft loss than those without it. However, dkGFR, dkCCr, body surface area ratio, recipient age, occurrence of glomerulopathy and HLA missmatch were not different. In multivariate analysis, donor age(p<0.05) and the experience of acute rejection(p<0.01) were independent factors affecting graft loss. We therefore conclude that donor age is more important as non-immunologic prognostic factors in graft dysfunction than GFR of the donated kidney and the difference in body mass between recipient and donor.

The Effect of Ratio of Kidney Weight to Recipient Weight and Body Surface Area on the Renal Allograft Outcome / 대한이식학회지

The hyperfiltration hypothesis postulates that kidney with reduced renal mass will progress toward failure due to hypertrophy of the remaining nephron to meet the excess load, eventually leading to nephron exhaustion. We assessed the influence of renal size on graft function in all allogrft except loss of graft within 6 month between September 1995 and February 1997(n=58). Patients were divided into two groups based on the ratio of kidney weight to recipient body surface area(KW/BSA>or=0.11, KW/BSAor=0.3, KW/BW<0.3) respectively and outcomes were compared by methods including student t-test and Chi-square test. Three conditions, in which hyperfiltration might be suspected, proposed by Teraski, were studied also: grafts from females to males compared with males to females, kidneys that experience rejection episodes and cadaveric grafts compared with living donor grafts. There was no correlation between KW/BSA, KW/BW and serum creatinine and degree of proteinuria at 1, 3, 6, 12 months posttransplant. Three conditions under which hyperfiltration damage might be suspected had no differences in study groups. Although more cases should be studied with long term follow-up, we conclude that donor kidney size has no apparent effect on renal allograft outcome in short term follow-up.