Association of Urinary Plasminogen-Plasmin with Edema and Epithelial Sodium Channel Activation in Patients with Nephrotic Syndrome.

BACKGROUND: Previous animal experiments and small human studies suggest that urinary plasmin can activate the epithelial sodium channel (ENaC) and contribute to sodium retention in nephrotic syndrome (NS), but this however is not well studied in clinical settings, and its relevance to edema formation is not well characterized in humans. We have investigated the association between urinary plasmin and clinical phenotypes in a large group of patients with NS from multiple etiologies, aiming to assess the role of urinary plasmin in sodium handling and edema formation. METHODS: Two hundred and three NS patients with urine and blood samples were divided into mild and severe symptom groups based on their edema severity. Twenty six of them had serial samples collected during the course of immunosuppressive therapy. The plasminogen-plasmin level and other key parameters were assayed, and their association with clinical manifestations were analyzed. RESULTS: One hundred and one of the 203 patients had renal biopsies performed, the results of which had included all the common types of primary NS and various types of secondary NS. Quantitative comparison and multivariate logistic regression analysis identified urinary plasminogen-plasmin to creatinine ratio (uPLG-PL/C), serum albumin, D-Dimer, and cardiac dysfunction history, but not albuminuria or 24-h urine protein, as independent risk factors for edema (p < 0.01). In patients who were treated and had serial samples, a decrease in uPLG-PL/C was identified as an independent influencing factor of edema remission (p < 0.01). Finally, the urinary fractional excretion of sodium (FENa) in patients was inversely correlated with the fractional excretion of potassium (FEK; p< 0.001), and FEK/FENa ratio was positively correlated with uPLG-PL/C (p < 0.001), suggesting a close association between uPLG-PL and ENaC activation. CONCLUSIONS: Our study identifies uPLG-PL abundance as an independent influencing factor of edema in adult NS patients, and supports the conclusion that plasmin-dependent ENaC activation is an important pathophysiological mechanism of sodium retention and edema formation in humans with NS.

Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema.

The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t­test or the Chi­square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1­positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2­positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1­AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS.

Renal Behçet's disease: an update.

OBJECTIVE: The aims of this study are (1) to report 33 patients with Behçet's disease (BD) having various renal manifestations, and (2) to update current data using our patients and published papers about BD and renal manifestations. METHODS: The PubMed database was searched using the terms BD or Behçet's syndrome. We found reports of 94 patients (including ours) with BD and specific renal diseases (amyloidosis, 39; glomerulonephritis [GN], 37; renal vascular disease, 19; interstitial nephritis, 1). RESULTS: The presentation of renal disease was edema/nephrotic syndrome in 12 patients (36%). Renal disease was incidentally diagnosed by routine urine analysis and measurement of serum creatinine level in 20 patients (61%). Renal failure was present in 23 patients (70%) and 5 of them have had cyclosporine treatment. The frequency of renal disease among BD patients has been reported to vary from less than 1 to 29%. CONCLUSIONS: The clinical spectrum of renal BD shows a wide variation. Amyloidosis (AA type), GN, and macroscopic/microscopic vascular disease are the main causes of renal BD. Patients with vascular involvement have a high risk of amyloidosis and amyloidosis is the most common cause of renal failure in BD. Several types of glomerular lesions are seen in BD. Current treatment options for renal BD are not evidence based. Radiological vascular intervention combined with immunosuppressive drugs can be useful in selected cases. Routine urine analysis and measurement of serum creatinine level are needed for early diagnosis of renal BD.

Epidemic dropsy: observations on pathophysiology and clinical features during the Delhi epidemic of 1998.

Epidemic dropsy results from the consumption of edible oils adulterated with Argemone mexicana oil by unscrupulous traders. Twenty consecutive 'in-door' patients of dropsy were intensively studied during the recent Delhi epidemic. Samples of edible oil used by them, their urine and their serum samples tested positive for sanguinarine on thin layer chromatography. The illness starts as a gastro-enteric illness followed by oliguria and pedal oedema. The following are often observed: cutaneous erythema with blanching and tenderness on pressure; violacious pigmentation of the skin; shortness of breath with orthopnoea; right-sided heart failure with normal left ventricle (LV) functions; as well as severe anaemia and hypoalbuminaemia. Renal function tests showed: bland urinary sediments; decreased glomerular filtration rate (GFR); mild to moderate azotaemia; acute tubular necrosis; patchy pneumonitis; moderate hypoxia with respiratory alkalosis; and restrictive ventilatory defects on blood gas analysis; and spirometry suggestive of interstitial pulmonary oedema of non-cardiogenic origin. 99mTc colloid sulphur liver scans showed colloid shift. There was marked dilatation and proliferation of dermal capillaries in the absence of significant inflammation in the biopsy specimens. Toxic alkaloids of Argemone mexicana oil induce widespread capillary dilatation and permeability causing leakage of protein rich plasma into the interstitial tissues of various organs. A hypovolaemic state is thus induced producing renal hypoperfusion which may progress to acute tubular necrosis. Interstitial fluid in alveoli causes restrictive ventilatory dysfunction with hypertension and right-sided failure with well-preserved LV function. The hepatic venous congestion induces Kupffer's cell dysfunction, which results in colloid shift on a radionuclide liver scan.

Malacoplaquia intestinal en pediatría: A propósito de un caso y revisión de la literatura / Intestinal Malacoplaquia

Se inform del caso de un niño de 13 años de edad hospitalizado en el Instituto Nacional de Salud del Niño, que ingresó con edema generalizado, diarrea crónica y hematoquezia. La biopsia de intestino estableció el diagnóstico de Malacoplaquia. A pesar del tratamiento instaurado la evolución clínica fué tórpida. Se revisa la literatura médica principalmente la relacionada al grupo pediátrico

Urinary and plasma cyclic adenosine 3',5'-monophosphate in patients with idiopathic edema.

Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone.

Spontaneous changes in weight, leg volume, renin, aldosterone and sex hormones in patients with cyclical oedema.

In four women with cyclical oedema related to the menstrual cycle, weight, leg volume, urinary excretion of sodium, aldosterone and oestrogens, plasma concentrations of progesterone, angiotensin II and plasma renin activity were measured at intervals during 4 weeks while they were taking a fixed sodium diet. In another patient, regular biphasic changes in weight and basal body temperature, disappearing after ovariectomy, were demonstrated. Changes in weight (varying between 3.5 and 5.5 kg) with corresponding changes in sodium balance were observed. In three patients, the maximum weight occurred in the second half, and in the other patient in the first half of the menstrual cycle. Plasms renin activity was in the normal range in all patients. It tended to rise when weight fell and vice versa. Aldosterone excretion behaved similarly and seems to be related to plasma progesterone in three patients. Orthostatic increase in leg volume did not significantly correlate with change in early morning weight. Thus, renin, aldosterone and orthostatic pooling of plasma fluid did not seem to be of primary importance in the pathogenesis of oedema in these patients. Oestrogen excretion in the luteal phase of the cycle was abnormally low in two patients; both had premenstrual oedema. In none of the patients could sodium retention be explained by excessive oestrogen and/or diminished progesterone production.