Histological and functional characteristics of peritoneal membrane in peritoneal sclerosis of PD patients.

BACKGROUND: Function and structure of peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). Peritoneal sclerosis is a common finding in peritoneal biopsies (PB) of PD patients. The aim of this study was to examine the impact of peritoneal sclerosis on peritoneal function and clinical parameters in PD patients submitted to peritoneal biopsy. METHODS: A PB was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. For each patient PM transport was evaluated by the last peritoneal equilibration test before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies. RESULTS: Patients with submesothelial sclerosis and those with impairment of submesothelial basement membrane and subendothelial vascular membrane were submitted to a larger daily glucose load. Peritoneal sclerosis > 50 microns was more frequent in high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. Mesothelial loss is correlated to peritoneal sclerosis and vascular injuries. CONCLUSIONS: Peritoneal sclerosis is not constant in PD patients: it is related to the loss of mesothelium integrity, to the daily glucose load of PD treatment and to vascular injuries, but apparently not to the presence of inflammatory infiltrate. It remains a matter of debate how much the peritoneal sclerosis modifies the function of PM and how new more biocompatible PD solutions could reduce PM injury.

Adducin polymorphism affects renal proximal tubule reabsorption in hypertension.

Abnormalities in renal sodium reabsorption may be involved in the development and maintenance of experimental and clinical hypertension. Adducin polymorphism is thought to regulate ion transport in the renal tubule. It has recently been shown that there is a significant linkage of alpha-adducin locus to essential hypertension and that the 460Trp allele is associated with hypertension. Patients with this allele display larger blood pressure changes with body sodium variation. The aim of this study was to test whether alpha-adducin polymorphism is involved in abnormalities of renal function. Because proximal tubular reabsorption has been shown to be tightly coupled to renal perfusion pressure, this segmental tubular function was investigated in 54 (29 Gly/Gly and 25 Gly/Trp) untreated hypertensive patients in basal conditions with the use of endogenous lithium concentration and uric acid. Fractional excretions of lithium and uric acid were significantly decreased in the Gly/Trp hypertensive patients compared with the Gly/Gly hypertensives. The contribution of alpha-adducin to fractional excretion of lithium was investigated by multiple regression analysis. Adducin genotype was significantly (R2=0.11, F=6.5; P<0.01) and directly related to fraction excretion of lithium; gender, age, urinary Na+, urinary uric acid, mean blood pressure, and plasma renin activity were not related. In conclusion, the adducin gene can be considered to be a 'renal hypertensive gene' that modulates the capacity of tubular epithelial cells to transport Na+ and hence contributes to the level of blood pressure.

Genetics of renal mechanisms of primary hypertension: the role of adducin.

PURPOSE: To summarize data concerning the identification of adducin as a 'candidate' gene in the Milan hypertensive strain of rats (MHS), a genetic model of essential hypertension, and in human essential hypertension. RESULTS: The sequence of events from renal function to cell membrane ion transports and finally to the molecular defect has been established in MHS rats. This led to the identification of polymorphisms in the cytoskeletal protein adducin. These polymorphisms are involved in blood pressure regulation in these rats. A linkage and an association study on Caucasian populations support the involvement of adducin in human hypertension also. A polymorphism of alpha-adducin gene is significantly associated with human hypertension. In particular, both in humans and in rats, adducin polymorphisms affect kidney function by modulating the overall capacity of tubular epithelial cells to transport ions. CONCLUSIONS: Adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.

Clinical aspects of peritoneal sclerosis.

Peritoneal sclerosis (PS) occurs in various clinical situations in Peritoneal Dialysis (PD) patients. Some degree of PS is often present in long-term PD patients, generally without clinical or functional consequences. At the other end of the spectrum of PS there is Sclerosing encapsulating peritonitis (SEP). Though infrequent, it is very severe. SEP is not a complication exclusive to PD; it is a syndrome related to many diseases of abdominal organs, some drugs and abdominal surgery. Remarkably, in many cases, the first symptoms of SEP appear months or years after the change from PD to HD has occurred. Today there is no full agreement about the microscopical findings of SEP or about the name of this syndrome: SEP or Encapsulating Peritoneal Sclerosis (EPS). The main etiopathogenetic factor for PS is the poor biocompatibility of PD solutions. In the etiopathogenesis of SEP, other factors in addition to the PD fluids have been suggested as possible causes (peritonitis, drugs, disinfectants, etc.). This paper reviews all the clinical aspects of PS and SEP: pathogenesis, clinical signs, diagnosis and therapy.

[Morpho-functional study of peritoneum in peritoneal dialysis]. / Studio morfo-funzionale del peritoneo in dialisi peritoneale.

BACKGROUND: Peritoneal dialysis (PD) impairs both structure and function of the peritoneal membrane (PM). Aim of the study is to examine the relationship among dialytic, histological and functional parameters in PD patients. METHODS: Thirty-one PD patients were submitted to peritoneal biopsy (PB) during catheter removal for malfunction or after dropping out of the treatment. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) prior to PB. Each daily glucose load was calculated. PB was performed at a distance of at least 5 cm from the catheter insertion point. The tissues were promptly embedded in formalin and stained for histological and immunohistochemical studies. RESULTS: 1) Patients with mesothelial impairment had longer treatment time. 2) Patients presenting submesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to larger daily glucose loads. 3) High transporters were exposed to larger daily glucose loads and presented an SS thickness greater than 50 micron more frequently than medium-high transporters. 4) Mesothelial loss was correlated with SS and vascular alterations. 5) SS and vascular injuries were related to each other and not to inflammatory infiltrate. CONCLUSION: Our study suggests that PD length seems to be mainly involved in mesothelial impairment; glucose load appears to damage mainly the submesothelial layer; SS is not a constant event in PD patients and in itself does not seem to be a decisive factor in PD drop out.

Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients.

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.