Pentosidine and its deposition in renal tissue in renal transplantation

BACKGROUND: Advanced glycation end products (AGEs) accumulate in lesions of arteriosclerosis, Alzheimer's disease, rheumatoid arthritis, diabetic retinopathy, and diabetic nephropathy. Among AGEs, chemical quantification and immunohistologic methods for pentosidine have been established. Free pentosidine-eliminated by renal excretion- is mainly affected by renal function. In this study, we measured concentrations of plasma free and total pentosidine and immunohistologically investigated kidney graft biopsy specimens in patients after renal transplantation to investigate the renal function, plasma free and total pentosidine, and its relationship with deposition in the renal tissue. PATIENTS AND METHODS: In 28 patients who underwent renal transplantation from 1996 to 2003, we measured the time course of plasma concentrations of free pentosidine, total pentosidine, and serum creatinine starting right after renal transplantation. Thirty-four graft biopsy specimens were immunohistologically investigated using anti-pentosidine antibody. Plasma free and total pentosidine, and serum creatinine were measured at the same time. RESULTS: Plasma free and total pentosidine were positively correlated with serum creatinine. Plasma free pentosidine and serum creatinine reached nadir values on day 34.2 +/- 14.2, when the blood concentrations were 5.1 +/- 1.6 pmol/mL and 1.7 +/- 0.7 mg/dL, respectively. Plasma total pentosidine reached a nadir on day 116.5 +/- 39.7 when the plasma concentration was 4.0 +/- 1.5 pmol/mg. We correlated the time required to reach the nadir of plasma free and total pentosidine concentrations. However, neither the concentration of plasma free nor plasma total pentosidine at nadir correlated with serum creatinine. The intensity of immunostaining with anti-pentosidine antibody in proximal tubular cells was graded as weakly positive, positive, or strongly positive. Significant differences were obtained among plasma free pentosidine values between the weakly positive and strongly positive groups. CONCLUSIONS: Renal transplantation improves renal function and decreases renal excretion of free pentosidine. Accordingly, total pentosidine also decreases. However, the concentrations of plasma free and total pentosidine at nadir varied among individuals; the blood concentrations were not determined by renal function alone. It was suggested that deposition of pentosidine in proximal tubular cells was more severe among patients with higher plasma free pentosidine and serum creatinine values.     

A sensitive and specific ELISA for plasma pentosidine.

BACKGROUND: Advanced glycation end products are formed by non-enzymatic glycation and oxidation reaction. Pentosidine is a well-known and characterized structure among them, and has been implicated in the pathogenesis of complications associated with chronic renal failure and long-term dialysis, such as dialysis-related amyloidosis and atherosclerosis. METHODS: We established a highly sensitive and specific competitive enzyme-linked immunosorbent assay (ELISA) for plasma pentosidine and applied it to large numbers of plasma samples including haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. We compared their plasma pentosidine levels determined by the competitive ELISA with those determined by high-performance liquid chromatographic (HPLC) assay currently used. RESULTS: The plasma pentosidine levels determined by the ELISA were correlated well with those determined by sophisticated instrumental HPLC assay, both in non-diabetic and diabetic dialysis patients. Both analyses yielded comparable results, with over 8-fold higher plasma pentosidine levels in HD and CAPD patients, irrespective of the presence or absence of diabetes, as compared to normal subjects and non-uraemic diabetic patients. CONCLUSIONS: The competitive ELISA will provide a rapid and convenient determination of plasma pentosidine content and thus be useful to assess the carbonyl stress in uraemic patients.     

Increased production of urea hydrogen peroxide from Maillard reaction and a UHP-Fenton pathway related to glycoxidation damage in chronic renal failure

Urea hydrogen peroxide (UHP) is a stable form of H(2)O(2) and cytotoxic agent. This study describes examination of UHP formation from collagen glycation and relevant glycoxidative damage in chronic renal failure (CRF). Renal fibers were incubated with 50 mM ribose in either serum ultrafiltrate or phosphate-buffered saline in the presence of various concentrations of urea. UHP was determined by a modified ferrous oxidation in xylenol orange (FOX) assay. The presence of urea resulted in an increase in the generation of UHP in a dose-dependent manner of urea in these incubation systems. Pentosidine levels analyzed by HPLC also increased in a dose-dependent manner of urea. Blocking experiments showed that pentosidine and carboxymethyllysine formation was significantly enhanced by hydroxyl radical generated from UHP via Fenton reaction. The renal and cardiac levels of UHP, pentosidine, and carboxymethyllysine in patients with CRF, including seven predialysis and eight hemodialysis subjects, were significantly higher than that in controls (n = 16). The renal and cardiac levels of UHP closely correlated with the levels of renal and cardiac pentosidine and carboxymethyllysine and inversely correlated with left ventricle ejection fraction in CRF patients. This study provides evidence, for the first time, that UHP can be produced from Maillard reaction. Increased UHP in chronic renal failure enhances the formation of pentosidine and carboxymethyllysine via Fenton reaction (UHP-Fenton pathway).     

Plasma advanced glycosylation end-products in maintenance haemodialysis patients

BACKGROUND.: Pentosidine is a useful marker of advanced glycation end-products(AGE) which form cross-links between proteins and have beenfound elevated in plasma and tissues of uraemic and haemo-dialysedsubjects. The origin and fate of these molecules are not clearlyunderstood, but they might play a role in the cardiovascularcomplications of end stage renal failure. The aim of this studywas to evaluate the effect of different types of substitutivetherapy on the removal of pentosidine. METHODS.: Pentosidine was measured by a two-step HPLC methodology. Itsconcentration was evaluated in plasma before and after dialysissession, in 24-h urine, and in dialysate of subjects treatedwith three types of chronic substitutive therapy: bicarbonatehaemodialysis, acetate-free biofiltration, and haemofiltration.Pentosidine levels were compared among the three therapy modalitiesand correlated with clinical and biochemical parameters. RESULTS.: Plasma pentosidine level was extremely high (23.7±2.0pmol/mg protein) in the patients treated with the differentdialysis modalities. The dialysis session had no significanteffect on its plasma concentration, but haemofiltration seemedto be the most efficient method (300–2000 nmol of pentosidineremoved per session versus 250–700 nmol per session withthe two other approaches). An interesting correlation was foundbetween pentosidine and blood urea nitrogen (r=0.58, P<0.01)and pentosidine with uric acid (r=0.48, P<0.05). CONCLUSIONS.: These results suggest that none of the methodology showed agood removal of pentosidine, but among them haemofiltrationhas the best efficiency. The statistical relationships betweenpentosidine and urea and uric acid respectively might provideinsight into the origin of pentosidine. The accumulation ofreactive AGE in uraemic patients may be implicated in the organand tissue damage observed in uraemia.     

Decreased fractional excretion of urate as an indicator of prerenal azotemia

Although the fractional excretion of uric acid (FEUA) is known to reflect extracellular fluid volume changes, the diagnostic significance of decreased FEUA in dehydration has not been previously reported. We studied the possible association between low FEUA and acute prerenal azotemia, and its diagnostic value, compared with other traditional indices, in discriminating prerenal azotemia from renal parenchymal causes of acute renal failure. In 65 chronic renal disease patients, 174 FEUA measurements were obtained from 24-hour urine collections. FEUA levels increased as reciprocal serum creatinine levels decreased. All 8 patients with prerenal azotemia showed significantly decreased FEUA values compared with chronic renal disease patients with a comparable degree of serum creatinine elevation, whereas all 7 patients with acute renal failure had FEUA values higher than those of chronic renal disease patients with comparable creatinine levels. FEUA values in prerenal azotemia were distinctly lower than those in acute renal failure (p less than 0.001). Patients with prerenal azotemia showed a lower fractional excretion of sodium, a lower fractional excretion of chloride and renal failure index, and a higher urine-to-plasma creatinine ratio than those with acute renal failure (p less than 0.05). However, these traditional indices were not useful in discriminating between the two conditions. The urine-to-plasma urea nitrogen ratio and the ratio of plasma urea nitrogen to creatinine showed no statistical difference between prerenal azotemia and acute renal failure. We conclude that, in acute azotemia, a decreased FEUA value may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure.     

Plasma exchange in Goodpasture's syndrome

The clinical course and levels of anti-glomerular basement membrane (GBM) antibody were compared in 20 patients with Goodpasture's syndrome treated with plasma exchange and immunosuppression (8 patients), immunosuppression alone (4 patients) or no specific therapy (8 patients). There was a more rapid fall in the level of anti-GBM antibody and pulmonary hemorrhage was less protracted in the 8 patients treated with plasma exchange and immunosuppression. In this group, 1 patient who presented with severe renal failure showed a marked improvement of renal function and there was no progression of disease in the 4 with milder renal involvement. 2 of the 4 patients treated with immunosuppression alone, and only 2 of the 8 patients who received no specific therapy, maintained normal renal function. In the group which received no specific therapy, 1 of the 6 patients who progressed to renal failure had mild renal involvement initially. There was a significant correlation between the level of anti-GBM antibody and the severity of the morphological changes seen at renal biopsy but not between the level of anti-GBM antibody and the severity of lung hemorrhage. The course and outcome of the disease in those patients not treated, or treated with immunosuppression alone, was better than that described in early reports of this disease, while those patients with plasma exchange and immunosuppression fared even better. An adequately stratified controlled trial of immunosuppression and plasma exchange versus immunosuppression alone is in order.     

Are the Anticardiolipin Antibodies a Risk Factor for Coronary Artery Disease in Chronic Renal Failure Patients?

Objective. It has been proposed that anticardiolipin (aCL) antibodies are a risk factor for coronary artery disease (CAD) in recently studies. In this study, we aimed to investigate the existence of coronary artery disease in dialysis patients who were aCL positive and undergoing hemodialysis and peritoneal dialysis due to end stage renal failure and also to determine its relationship with risk factors in patients with coronary artery disease. Methods. This study has been conducted in the end stage renal failure in 140 hemodialysis patients, 18 peritoneal dialysis patients, and 38 healthy controls. The urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin values are obtained. In all cases, aCL levels are investigated with ELISA method. Results. In the HD and CAPD patients, no significant relationship could be found between the age, gender, dialysis time, total cholesterol, HDL cholesterol, LDL cholesterol, total protein, and albumin values (p > 0.05). HD and CAPD vs. controls (aCL), 9.2% (13/140), 11.1% (2/18) vs. 2.6% (1/38), p = 0.002. No significant difference was noted between aCL-positive and -negative patients in serum urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin levels. The coronary artery disease was determined in three patients out of 16 patients with aCL positivity. Conclusion. The prevalence of aCL antibodies positivity in our study was similar to the prevalence of aCL positivity in other studies. Therefore, we do not think aCL antibodies positivity is a risk factor for coronary artery disease.     

125I-iothalamate and creatinine clearances in patients with chronic renal diseases.

In 196 adult patients with chronic renal disease or primary hypertension, the evaluation of glomerular filtration rate (GFR) by means of creatinine clearance, 'predicted' creatinine clearance and [125I]-iothalamate clearance was performed. Iothalamate clearance was evaluated after subcutaneous injection of the substance . In patients with normal or upper borderline plasma creatinine values, the iothalamate clearance ranged from 44 to 117 ml/min/1.73 m2 and the overestimation of GFR from creatinine clearance was negligible. In patients with mild or advanced renal failure, the overestimation of GFR from creatinine clearance increased up to 18 and 32%, respectively. The clinical usefulness of iothalamate clearance is evident especially in patients with mild renal failure, in whom an accurate evaluation of GFR is often important for a correct dietary and therapeutic approach.     

High plasma pentosidine level is accompanied with cardiovascular events in hemodialysis patients

Background

Cardiovascular disease is a major complication in patients with end-stage renal disease (ESRD). The accumulation of advanced glycation end products (AGEs) is facilitated in these patients. The aim of this study was to investigate the relationship between circulating AGEs and cardiovascular events in hemodialysis patients.

Methods

The plasma level of pentosidine, a well-defined AGEs, was measured in 110 hemodialysis patients who were prospectively followed for 90?months. The relationship between plasma pentosidine level and cardiovascular events was assessed using Kaplan-Meier and Cox regression analysis.

Results

Thirty-nine cardiovascular events (14 coronary heart disease and 25 strokes) occurred during the follow-up period. Multivariable Cox proportional hazard analysis showed that plasma pentosidine levels (HR 1.040, 95% CI 1.022–1.058, p?p?p?Conclusion The plasma pentosidine level predicts cardiovascular events in hemodialysis patients. The effects of lowering circulating AGE levels on cardiovascular events should be examined in ESRD patients.     

Prediction of mortality in patients with bacteremia: the importance of pre-existing renal insufficiency

Pre-existing renal insufficiency serves as a common risk factor in the development of acute renal failure. Acute renal failure is a common finding in patients with bacteremia and is associated with poor prognosis. A total of 2722 consecutive patients 18 years old or older, fulfilling strike criteria of bacteremia or fungemia were prospectively evaluated to establish the prognostic importance of pre-existing renal insufficiency in bacteremic patients. They were classified according to serum creatinine levels upon admission into three groups. 915 patients had normal creatinine levels (< or = 1.0 mg/dL), 1528 had mild to moderate renal failure (creatinine 1.1-3 mg/dL) and 279 patients had severe renal failure upon admission (creatinine > 3.0 mg/dL). Mild to severe renal failure upon admission was associated with old age, male gender, diabetes mellitus, ischemic heat disease, hypertension and congestive heart failure. The serum albumin in patients with severe renal failure was significantly low, with a mean of 2-9 mg/dL. Urinary tract infections were more prevalent in patients with mild to severe renal failure, while intravenous line infections, bacterial endocarditis and soft and skin tissue infections were more common in patients with normal renal function. In the 279 patients with severe renal failure the mortality rate was significantly higher (50%) compared to patents with mild to moderate renal failure and patients with normal renal function (21% and 26% respectively, p = 0.0001). Multiple regression analysis revealed that pre-existing serum creatinine > 3 mg/dL was significantly associated with death attributable to bacteremia (OR = 1.7, 95% CI 1.0-2.7). In conclusion, adult bacteremic patients with pre-existing serum creatinine above 3 mg/dL upon admission are at increased risk of mortality due to bacteremia than patients with normal or mild to moderate renal failure.     

Relationship between vitamin A and bone disease in chronic renal failure

A study has been made of possible interrelationships between circulating vitamin A concentration and indicators of altered calcium homeostasis in 31 patients with stable chronic renal failure. Plasma retinol concentrations were high, possibly as a result of increased retinol-binding-protein concentrations secondary to renal failure. There was no correlation between retinol concentration and any other measurement, including vitamin A intake. However, there were significant correlations between plasma parathyroid hormone and calcium, phosphate, alkaline phosphatase, urea, and creatinine concentrations; and those patients with radiological sub-periosteal erosions tended to have the highest concentrations of circulating parathyroid hormone. Our data give no support to the contention that vitamin A status has any bearing on the progression and severity of the hyperparathyroid bone disease of renal failure.     

Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy

Pentosidine is an advanced glycation end-product (AGE), formed by glycosylation and oxidation, that accumulates markedly in end-stage renal disease (ESRD). It has been speculated that AGE and carbonyl stress contributes to long-term complications such as cardiovascular disease (CVD) in ESRD patients. This study determined plasma levels of pentosidine as well as the presence of inflammation (CRP > or = 10 mg/L), clinical CVD (CVD(clin)), and malnutrition (subjective global assessment [SGA] > 1) in a cohort of 191 ESRD patients, median age of 55 yr (range, 23 to 70 yr) and median GFR = 7 ml/min (range, 2 to 17 ml/min), close to start of renal replacement therapy. Fifty-one elderly subjects, median age of 82 yr (range, 71 to 110 yr), with mild renal impairment, median GFR = 67 ml/min (range, 38 to 113 ml/min), were also studied for comparative analysis of plasma pentosidine. The plasma pentosidine content was elevated in all patients compared with the levels in the elderly subjects and were negatively correlated with GFR both in the ESRD patients (Rho = -0.24; P < 0.01; n = 159) and in the elderly subjects (Rho = -0.31; P < 0.05). Moreover, the plasma pentosidine content was correlated with age in the ESRD patients (Rho = 0.26; P < 0.001) and in the elderly subjects (Rho = 0.44; P < 0.001). The 63 malnourished ESRD patients (35%) had a significantly higher (P < 0.05) median plasma pentosidine than the well-nourished patients (39 versus 27 pmol/mg albumin). Similarly, 73 inflamed patients (38%) had a significantly higher (P < 0.001) median pentosidine content compared with 118 non-inflamed patients (37 versus 24 pmol/mg albumin). Also, the plasma pentosidine content showed weak but significant positive correlations with CRP (Rho = 0.28; P < 0.0001), fibrinogen (Rho = 0.23; P < 0.01; n = 126), IL-6 (Rho = 0.22; P < 0.01; n = 169), and soluble vascular cellular adhesion molecule-1 (Rho = 0.38; P < 0.001; n = 74). On the other hand, no significant differences in plasma pentosidine content were noted between the patients with and those without CVD(clin) (32 versus 27 pmol/mg albumin, respectively). Analyses of all-cause mortality, by Kaplan-Meier, showed that mortality was not linked to the plasma pentosidine content. Moreover, survival analysis by the Cox regression model showed that age (P < 0.001), diabetes mellitus (P < 0.01), malnutrition (P < 0.01), and CVD(clin) (P < 0.01) independently predicted poor outcome, whereas an elevated plasma pentosidine content did not. The present study shows that an elevated plasma pentosidine content in ESRD patients is significantly associated with both inflammation and malnutrition and confirms that low residual renal function and high age further contribute to an increased plasma pentosidine content. However, in this small cohort, the plasma pentosidine content did not predict outcome. Thus, accumulation of plasma pentosidine is unlikely to be an appropriate clinically useful marker to predict mortality in ESRD patients.     

Intraperitoneal rupture of the bladder causing the biochemical features of renal failure

A group of 20 patients with intraperitoneal rupture of the bladder was compared with a group of 20 patients with haematuria due to renal injury. In patients admitted to hospital within 24 h of sustaining an intraperitoneal bladder rupture, the mean serum levels of creatinine and potassium were increased and the mean serum sodium level was decreased. However, the individual serum creatinine values were within normal limits in six of the 11 patients in this group. Patients presenting more than 24 h after intraperitoneal bladder rupture had an increased mean serum urea, creatinine and potassium level and a decreased mean serum sodium and CO2 content. The individual serum urea and creatinine values on admission to hospital were higher than normal in all nine patients in this group but the serum urea/creatinine ratio was not significantly elevated. A dramatic decrease in serum urea and creatinine levels was seen within 24 h after laparotomy and suturing of the bladder rupture. In patients with abdominal symptoms and signs, haematuria and the biochemical features of renal failure (elevated serum urea, creatinine and potassium, decreased serum sodium and CO2 content), the clinician should suspect an intraperitoneal rupture of the bladder.     

Intravenous pyelography in nonuremic diabetic patients

We studied the influence of intravenous pyelography (IVP) in 40 diabetic patients with a serum creatinine level of less than 2 mg/100 ml. None of the patients experienced irreversible renal function changes but 4 patients had an early significant rise in creatinine levels (greater than 0.2 mg/100 ml). In 3 of these it was only mild, but 1 patient sustained reversible serious damage with a creatinine rising from 1.6 to 3.8 mg/100 ml. 3 of these 4 patients had evidence of renal disease with mild creatinine elevations or proteinuria. Thus, IVP is a relatively safe procedure in nonuremic diabetic patients. This is different from IVP in diabetic patients who have creatinines over 2 mg/100 ml where 76% of the patients have serious acute renal failure and this is irreversible in one-third.     

High proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) level measured by the capture enzyme-linked immunosorbent assay method is associated with decreased patient survival in ANCA-associated vasculitis with renal involvement

Wegener granulomatosis (WG) and microscopic polyangiitis (MP), diseases associated with antineutrophil cytoplasmic antibodies (ANCA), had an extremely poor prognosis before the introduction of cyclophosphamide and corticosteroids for their treatment. However, there is still reduced patient survival, and some studies have documented severe side effects of the immunosuppressants used. This 10-yr follow-up study assessed 117 consecutive patients with WG or MP with biopsy-confirmed renal involvement. The cumulative relative patient survival was lower: 0.664 for women and 0.648 for men. The causes of death (n = 64) were in most cases registered as associated with the vasculitic disease. Analysis of possible predictive factors for patient survival by multiple Cox regression analysis revealed that a very high level of proteinase 3 (PR3)-ANCA measured by the capture ELISA method, a diagnosis of MP, and older age were factors predicting poorer patient survival. High levels of B-thrombocytes at time of diagnosis were associated with a better prognosis. For patients surviving the first year, remission-sustaining therapy with azathioprine for longer than 12 mo was associated with improved patient survival. Thirty-nine patients developed end-stage renal failure. Elevated serum creatinine at time of diagnosis and a very high level of PR3-ANCA by capture ELISA were factors predicting a higher risk for renal failure during follow-up. The epitope on PR3 assessed by capture ELISA needs to be further analyzed and explored: it seemed to implicate poorer patient and renal survival in WG or MP with renal involvement.     

Proteinuria in IgA nephropathy

Clinicopathological data in 74 patients with IgA nephropathy were analyzed with special attention to level of proteinuria and its prognostic significance in this disease. Excretion rates exceeding 3 g per day (heavy), in the range of 1 to 2.9 g (moderate) and under 1 g per day (mild) each occurred in approximately equal proportions of patients. One-sixth of those with more than 1 g developed end-stage renal failure, while serum creatinine never exceeded 2 mg/dl in any with mild proteinuria. "Renal survival" (serum creatinine of 2 mg/dl or less) at five years after presentation was 100% in patients with persistently mild proteinuria, 87% in those whose protein excretion reached the moderate range, and 69% when heavy or nephrotic range proteinuria developed. Of significance, only rarely did mild proteinuria at presentation increase to higher levels. A correlation existed between level of protein excretion and severity of mesangial, segmental or global proliferation, glomerulosclerosis, podocyte effacement, interstitial infiltration, tubular atrophy and vascular sclerosis, even in patients with unimpaired renal function. Moderate or heavy proteinuria typically preceded the onset of hypertension and occurred prior to the development of renal insufficiency. Our results underscore magnitude of proteinuria as an early marker of glomerular damage in the prognosis of IgA nephropathy.     

Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature

Primary IgA nephropathy is generally considered an indolent disease, but progression to chronic renal failure is not uncommon, and a rapidly progressive course is observed in some cases, especially when extensive fibrocellular crescents are present. The therapeutic benefit of immunosuppression and plasma exchange remains controversial. We described two patients with primary IgA nephropathy and rapidly progressive renal failure. Both patients showed extensive glomerulosclerosis and crescent formation in their renal biopsies. Corticosteroid and immunosuppressive therapy failed to control the progression of the disease, and plasma exchanges were performed. In both cases, the serum creatinine and creatinine clearance initially improved with plasma exchange and the rapid progression of renal failure was apparently halted. In one patient, the serum creatinine rose when treatment was discontinued and fell again when plasma exchange was recommenced. Nevertheless, the long-term benefit of plasma exchange in crescentic IgA nephropathy was unsatisfactory as the renal function continued to deteriorate in the following 12 months despite an initial stabilization.     

Phenylacetylglutamine and hippuric acid in uremic and healthy subjects

Phenylacetyglutamine (PAG) and hippuric acid (HA) were determined in protein-free filtrates of plasma and urine from patients with chronic renal failure and healthy subjects, using reverse phase high performance liquid chromatography. Plasma accumulation of the metabolites was detected when the creatinine clearance was below 15 ml/min. Protein-binding studies showed that PAG was not bound to plasma proteins but that HA was partly bound. Concentrations of PAG and free HA in plasma did not correlate with values of serum urea or creatinine. Hemodialysis decreased the plasma concentration of PAG and free HA to about the same extent as that of urea and creatinine. The average renal clearances of PAG and HA were about 1.4 and 5 times higher, respectively, than the creatinine clearance. The daily excretion rates of PAG, HA, urea, and creatinine were similar in non-dialysis patients with a creatinine clearance higher than 15 ml/min and in healthy subjects, whereas patients with a creatinine clearance below 15 ml/min had lower excretion rates of urea, creatinine, and HA. However, the average excretion rate of PAG was in the same range in uremic and healthy subjects. The excretion rate of HA, but not of PAG, correlated with that of urea and creatinine.     

Natriuretic peptide and adrenomedullin levels in chronic renal failure and effects of peritoneal dialysis

Plasma levels of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-BNP) are elevated in renal impairment and provide a robust prognostic index. The effect of peritoneal dialysis on plasma NT-BNP, however, is unknown. Furthermore, no information exists regarding levels of the N-terminal propeptide for C-type natriuretic peptide (NT-CNP) in renal failure and the effects of peritoneal dialysis. Accordingly, we documented venous levels of these peptides, and adrenomedullin, across peritoneal dialysis. We measured venous BNP, NT-BNP, NT-CNP, adrenomedullin, blood urea nitrogen (BUN) and creatinine before, during and after completion of overnight peritoneal dialysis in 11 patients, and identical sampling was carried out in eight patients (controls) but between peritoneal dialysis treatments. Peptide levels were measured using well-validated, published methods. Baseline levels of NT-CNP (212, 150-303 pmol/l, median and 25th and 75th percentiles) were much higher than recorded previously in healthy volunteers or in heart failure, and correlated with plasma creatinine (rs=0.53, P<0.05). Peritoneal dialysis had no effect on plasma NT-CNP, nor on NT-BNP, BNP or adrenomedullin (all elevated above normal), whereas both BUN and creatinine levels, as expected, declined (P<0.001). We conclude that plasma levels of NT-CNP are grossly elevated in chronic renal failure and correlated with plasma creatinine, but are not altered by peritoneal dialysis. Likewise, BNP, NT-BNP and adrenomedullin are elevated but are not altered by peritoneal dialysis. This information is needed if levels of these hormones are to be used as prognostic indicators or as a guide to the management of patients with chronic renal failure.     

Advanced glycation end products in children with chronic renal failure and type 1 diabetes

Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nɛ-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P<0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P<0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabe-tic children showed significantly elevated pentosidine levels (P<0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics. Received: 25 July 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001