Pathological Proteinuria Research Articles

Effects of antihypertensive drugs on blood pressure and proteinuria in childhood

Historically, there have been few drug trials for antihypertensive treatment in childhood and recommendations have been extrapolated from data obtained in adulthood. During the last decade an increased awareness of the risks of childhood hypertension stimulated clinical trials of antihypertensive agents in children. The aim of this article is to systematically review the studies published between 1995 and 2006 that deal with the effect of antihypertensive drugs on childhood hypertension or proteinuria. Medline, Current Contents, personal files and reference lists were used as data sources. Fifty-two out of 79 initially found reports were excluded. Consequently 27 articles were retained for the final analysis. The blood pressure reduction was similar with angiotensin-converting enzyme inhibitors (10.7/8.1 mmHg), angiotensin II receptor antagonists (10.5/6.9 mmHg) and calcium-channel blockers (9.3/7.2 mmHg). In addition angiotensin-converting enzyme inhibitors (by 49%) and angiotensin II receptor antagonists (by 59%) significantly reduced pathological proteinuria. The blood pressure reduction of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and calcium-channel blockers is almost identical. In children with pathological proteinuria angiotensin-converting enzyme inhibitors or angiotensin II antagonists are superior to calcium-channel blockers.

Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis

Streptococcal pyrogenic exotoxin B is an extracellular cysteine protease. Only nephritis-associated strains of group A streptococci secrete this protease and this may be involved in the pathogenesis of post-streptococcal glomerulonephritis. Mice were actively immunized with a recombinant protease inactive exotoxin B mutant or passively immunized with exotoxin B antibody. Characteristics of glomerulonephritis were measured using histology, immunoglobulin deposition, complement activation, cell infiltration, and proteinuria. None of the mice given bovine serum albumin or exotoxin A as controls showed any marked changes. Immunoglobulin deposition, complement activation, and leukocyte infiltration occurred only in the glomeruli of exotoxin B-hyperimmunized mice. One particular anti-exotoxin B monoclonal antibody, 10G, was cross-reactive with kidney endothelial cells and it caused kidney injury and proteinuria when infused into mice. This cross-reactivity may be involved in the pathogenesis of glomerulonephritis following group A streptococcal infection.

Patients With Biallelic Mutations in the Chloride Channel Gene CLCNKB: Long-Term Management and Outcome

Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (<or=2.0 standard deviation score in 6 patients) significantly increased (P < 0.05) at the end of follow-up in comparison to values at diagnosis. Nonpostural persistent proteinuria was present in 6 patients, and 4 patients had a glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s). These data show that some patients with biallelic mutations in the chloride channel gene CLCNKB tend to present with pathological proteinuria and impaired kidney function after a median follow-up of 14 years, and growth retardation is common and sometimes related to growth hormone deficiency in these patients.

Enzyme Replacement Therapy and Fabry Kidney Disease

for agalsidase alfa is 0.2 mg/kg and for agalsidase beta it is 1.0 mg/kg body weight. Approval for both agents was based on Orphan Drug provisions with the use of surrogate end points, 8 such as clearing of vascular endothelial deposits, 11 and symptomatic improvement of pain scores. 12 Furthermore, when ERT was initiated in patients with relatively mild disease, there appeared to be favorable responses in terms of slowing or preventing serious organ dysfunction. 12,13 Less favorable results have been reported in open-label, longitudinal studies in patients with more advanced kidney disease, particularly with overt proteinuria. 14,15 These concerns are echoed by the recently published results of a Phase IV, randomized, prospective, placebo-controlled trial, in which 82 patients with initial glomerular filtration rate (GFR) values 55 mL/min/1.73 m 2 did quite well compared with their placebo control group, but those with more severe disease and proteinuria were not as clearly benefited by ERT. 16 Interpretation of this study is complicated by a baseline imbalance in the urine protein excretion between the placebo group and the agalsidase beta group, 16 and the relatively small number of patients included in what was designed to be an outcome study. 17 Proteinuria has emerged as an important risk factor for progression of kidney involvement in a number of kidney diseases, 18 including Fabry disease. 13 The significance of proteinuria in patients with Fabry disease and the limitations of ERT in addressing this issue have recently been examined. A common thread in all of the published outcome studies with agalsidase alfa 15,19 and agalsidase beta 11,13,14,16,20 is that ERT at the currently approved doses simply does not impact urinary protein excretion. The association between pathologic changes (eg, focal and global glomerular sclerosis, tubular atrophy, interstitial fibrosis) and proteinuria is not surprising. 20,21 To date, however, there has been no systematic attempt to reduce the proteinuria and slow the progression of kidney GFR decline in Fabry disease with antiproteinuric therapy, as has been so successful in type 1 and type 2 diabetes mellitus and other forms of proteinuric kidney disease. 22,23 A number of patients in the various trials 11,13‐16,19,20 were treated with angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs), but in none of these studies was systematic reduction of urinary protein excretion identified as a primary or secondary objective. 16 Post hoc analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan Study would stongly support the primary goal of reducing urinary protein and albumin excretion to a target level, perhaps even more importantly than achieving a fixed goal for systolic

A Dipstick Protein and Specific Gravity Algorithm Accurately Predicts Pathological Proteinuria

A Dipstick Protein and Specific Gravity Algorithm Accurately Predicts Pathological Proteinuria

Microalbuminuria and tubular proteinuria as risk predictors of cardiovascular morbidity and mortality in essential hypertension: final results of a prospective long-term study (MARPLE Study)*

To evaluate the impact of microalbuminuria (MAU) or tubular proteinuria (TPU) on cardiovascular and cerebrovascular events and all-cause mortality, and to assess whether a normalization of MAU and/or TPU induced by angiotensin-converting enzyme-inhibitor-based antihypertensive treatment with ramipril improves cerebrovascular prognosis in essential hypertensive patients without diabetes mellitus. A prospective, controlled, multicenter study was performed involving 3529 hypertensive participants (average follow-up 42.5 months). Ramipril was the basic antihypertensive medication. Proteinuria analysis (albumin, alpha 1-microglobulin, SDS electrophoresis) was performed by quantitative measurement every year. Ambulatory blood pressure monitoring was performed once yearly. The main outcome determined was cardiovascular and cerebrovascular events and all-cause mortality. In patients with TPU and/or MAU, the risk for endpoints increased significantly compared with normal (TPU, 30.0%; MAU, 54.7%; MAU + TPU, 64.0%; macroproteinuria, 74.4%). A change of protein excretion either from pathologic to normal or from normal to pathologic showed a clear trend to correlate with cerebrovascular endpoints (P = 0.056 and P = 0.055). Normal protein excretion at baseline and during follow-up indicated a significantly better prognosis than pathologic proteinuria at baseline and during follow-up. (P < 0.0001). TPU normalized in 31.9%, MAU in 30.6%, MAU + TPU in 29.3%, and macroproteinuria in 10.2% of patients. A total of 445 (25.4%) patients with normal protein excretion developed pathologic proteinuria during follow-up. In non-diabetic hypertensive patients, MAU as well as TPU increases the incidence of cardiovascular events. Normalization of MAU, TPU or macroproteinuria during angiotensin-converting enzyme-inhibitor-based treatment correlates with a reduction of cardiovascular events. Beyond blood pressure control, normalization of MAU and TPU should be considered as a further therapeutic goal. There is a need for further studies to optimize treatment if proteinuria is unresponsive to angiotensin-converting enzyme inhibitors.

New Potential Agents in Treating Diabetic Kidney Disease

Despite the worldwide epidemic of chronic kidney disease complicating diabetes mellitus, current therapies directed against nephroprogression are limited to angiotensin conversion or receptor blockade. Nonetheless, additional therapeutic possibilities are slowly emerging. The diversity of therapies currently in development reflects the pathogenic complexity of diabetic nephropathy. The three most important candidate drugs currently in development include a glycosaminoglycan, a protein kinase C (PKC) inhibitor and an inhibitor of advanced glycation. In targeting primary mechanisms by which hyperglycaemia contributes to diabetic complications, these drugs could provide risk reduction complementary to the partial reduction proven for ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers). Glycosaminoglycans act to restore glycoproteins present in reduced amounts in the glomerular basement membrane and mesangium of diabetic animal models. Components of the drug sulodexide prevent pathological changes and proteinuria in diabetic rats. Reductions in albuminuria, a hallmark of early diabetic kidney disease, have been reported in initial human trials. In the US, a multicentre phase II study has been completed, with an interim analysis indicating reduction in urinary albumin losses. Pivotal phase II trials have begun in patients with type 2 diabetes. A second metabolic pathway of diabetic complications is overexpression of PKC. Several activators of this family of intracellular kinases have been identified and PKC activation may result in tissue damage through a variety of mechanisms. In animal models, the inhibitor ruboxistaurin reduces albuminuria, diabetic histological changes and kidney injury. Like sulodexide, drug development of ruboxistaurin has reached completion of a phase II evaluation with mixed results. The third metabolic target is the nonenzymatic formulation of advanced glycation end-products (AGEs) through well described biochemical pathways. Multiple pathways lead to AGE accumulation in tissues in diabetes and diverse AGE products are formed. AGE deposition has been implicated in animal models of diabetic nephropathy. The leading AGE inhibitor currently in development is pyridoxamine, which has multiple actions that inhibit glycation. Pyridoxamine is an efficient AGE inhibitor in experimental diabetes. A phase II study in diabetic patients with nephropathy reported mixed efficacy results and a favourable safety profile. Phase III evaluation of pyridoxamine has not begun. These three classes of potential therapies, if successfully developed, will confirm that diabetic kidney disease has entered the era of biochemical treatments.

Comparison between 24‐h proteinuria, urinary protein/creatinine ratio and dipstick test in patients with nephropathy: Patterns of proteinuria in dipstick‐negative patients

Objective. Three main tests are commonly employed for the measurement of proteinuria: the dipstick test, the urinary protein/creatinine ratio (P/C) and the 24‐h urine collection. The aim of this study was to evaluate the correlation between these methods, comparing linear regression and ROC curve data. Material and methods. A total of 297 consecutive outpatients with different renal diseases were included in the study. Twenty‐four‐hour proteinuria was considered the reference test. Results. A high degree of correlation was observed between all the tests (p<0.0001), the highest regression coefficient being between 24‐h proteinuria and P/C (R = 0.82), and the lowest between P/C and the dipstick test (R = 0.72). The dipstick test failed to detect pathological proteinuria in 94 patients (31.6 %). Therefore, in these subjects, the patterns of proteinuria were assessed by immunofixation and sodium dodecyl sulphate (SDS) electrophoresis. Conclusions. Our data strongly support the use of urinary P/C for the detection of proteinuria, at least in nephrology units, where the prevalence of proteinuria is likely to be high.

Renal ultrasound findings in an Australian Aboriginal population with high rates of renal disease

Rates of albuminuria and haematuria are extremely high with haematuria prevalence as high as 30-50% in adults of some Aboriginal groups. Dipstick testing of urine is routinely carried out in Aboriginal communities and as part of school screening programmes. Evaluation of the many affected individuals has traditionally included renal ultrasound examination, which involves considerable expense and logistic problems in remote communities. The present study was conducted to evaluate the usefulness of ultrasound in this setting. A population survey was conducted in a remote community. Urine dipstick analysis and the albumin:creatinine ratio (ACR; g/mol) were measured in 1440 people over 5 years of age (89% of the eligible population), and a detailed renal ultrasound examination was performed in a random subset of 647 people (41.1% of the whole group), 276 aged 5-19 years and 371 over 20 years of age. Urine dipstick proteinuria (>1+) was present in 8.5% (23/271) of those aged 5-19 years and 37.9% (132/348) in those aged over 20 years; pathological albuminuria (ACR>3.4) was present in 7.6% (21/276) and 54.7% (203/371), respectively, and isolated haematuria was present in 7.7% (21/273) and 11.5% (40/347), respectively. Eight ultrasound abnormalities were found. Ultrasound findings did not change the management of any individual. Renal ultrasound added little to the evaluation of people with asymptomatic proteinuria or haematuria in this setting. In this scenario, ultrasound examination could be reserved for the cases with an unusual presentation where findings are likely to influence the prognosis or treatment, or in preparation for a renal biopsy.

A Dipstick Protein and Specific Gravity Algorithm Accurately Predicts Pathological Proteinuria

The proper strategy to screen for early chronic kidney disease is debatable, but protein-creatinine ratio from a random urine sample (UPC) commonly is used. The purpose is to determine whether dipstick data effectively identify patients with increased UPC ratios. Because urine concentration affects proteinuria interpretation, we hypothesized that dipstick protein (DSP) and specific gravity (SG) are sufficient for screening. A hospital laboratory database was searched for urine samples simultaneously assayed for UPC ratio, DSP, and SG (n = 2,098). A random 70% of the cohort was used to generate a development model, which was validated in the remaining 30%. Samples were stratified according to DSP and SG values. A DSP versus SG matrix was created, and each sample was allocated to a discrete DSP-SG category. Proportions of samples with overt (UPC ratio > or = 500 mg/g) and nephrotic-range proteinuria (UPC ratio > or = 3,000 mg/g) were calculated for all 40 cells. Optimum correlations between DSP-SG cells and UPC ratios were determined for the development model, yielding 97.0% negative predictive value (NPV) for a UPC ratio of 500 mg/g or less and 97.5% positive predictive value (PPV) for a UPC ratio of 500 mg/g or greater. NPV for a UPC ratio of 3,000 mg/g or less was 99.7%. Application of the model to the validation sample showed a 96.5% NPV for a UPC ratio of 500 mg/g or less, 99.4% PPV for a UPC ratio of 500 mg/g or greater, and 99.0% NPV for a UPC ratio of 3,000 mg/g or less. DSP and SG values effectively identify patients requiring proteinuria quantification by means of UPC ratio. A Web-based tool was developed that allows DSP and SG value entry and provides a recommendation regarding the need for proteinuria quantification.

Experimental autoimmune Goodpasture's disease: A pathogenetic role for both effector cells and antibody in injury

Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury. Active experimental autoimmune glomerulonephritis (EAG) was induced by immunization with alpha3-alpha5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (mu chain-deficient) mice. Passive disease was induced by transferring sera from B cell intact and B cell deficient mice with EAG to RAG-1-/- mice (that lack adaptive immunity). Histologic and functional injury was studied. Despite the absence of B cells and immunoglobulin in B-cell-deficient mice, histologic and functional injury developed in mice immunized with alpha3-alpha5(IV)NC1, with T cells and macrophages in glomeruli. Injury occurred to a similar degree to that found in B-cell-intact mice. Transfer of sera from B-cell-intact mice with EAG containing antibodies (but not from B-cell-deficient mice with EAG) to RAG-1-/- mice induced linear immunoglobulin deposits on the glomerular basement membrane (GBM) and pathologic proteinuria. Both cell-mediated and humoral effectors are capable of inducing renal injury in EAG. Given the similarity of the disease-initiating antigen in this model to the antigen in human anti-GBM glomerulonephritis, similar overlapping mechanisms are likely to operate in human disease.

Angiotensin-converting enzyme gene polymorphism in preeclampsia and normal pregnancy

Objective The purpose of this study was to evaluate the angiotensin-converting enzyme gene polymorphism in pregnant women with and without preeclampsia. Study design Preeclampsia was defined as hypertension and pathologic proteinuria in pregnant women after gestational week 20. Genomic DNA was isolated from leukocytes. The insertion-deletion polymorphism in intron 16 of the angiotensin-converting enzyme gene was detected in DNA samples with the use of the polymerase chain reaction. Chi-squared and Student t tests were used for statistical analysis. Results In preeclampsia (n = 51 women) angiotensin-converting enzyme genotypes were deletion-D (DD) in 16 women (31%), insertion-I (II) in 12 women (24%), and insertion-deletion in 23 women (45%); in the control group (n=71), the angiotensin-converting enzyme genotypes were DD in 21 women (30%), II in 17 women (24%), and insertion-deletion in 33 women (46%). Angiotensin-converting enzyme genotype distribution and allelic frequencies were not different between groups. Conclusion No difference in the angiotensin-converting enzyme genotype distribution was found between preeclampsia and normal pregnancy. The results showed no association between angiotensin-converting enzyme polymorphism and the development of preeclampsia.

Ramipril in the treatment of hypertension and proteinuria in children with chronic kidney diseases

Background Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension. The efficacy and safety of ramipril in adults has been proved; however, data on effectiveness of ramipril in children are few. The aim of the present study was to investigate the effect of ramipril on blood pressure (BP) and proteinuria in children with chronic kidney diseases. Methods A total of 31 children (median age 11.3 years, range 1.9–19.8 years) with various chronic nephropathies and hypertension or proteinuria were prospectively treated with ramipril for 6 months. Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children. Proteinuria was defined as protein excretion ≥100 mg/m 2/24 h. The starting dose of ramipril was 1.5 mg/m 2/24 h once daily. In 27 children it was given as monotherapy. Results The median decrease in ambulatory BP was 11 mm Hg for daytime systolic, 10 mm Hg for daytime and nighttime diastolic, and 8 mm Hg for nighttime systolic BP. Hypertension normalized in 55% of the children. Proteinuria decreased in 84% of the children with pathologic proteinuria; the median decrease was 51%. A positive correlation was found between initial proteinuria and change of proteinuria ( r = 0.95, P < .001). Glomerular filtration rate and serum potassium level did not change significantly. One child developed a cough that was believed to be related to ramipril. Conclusions Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension, proteinuria, or both.

Surveillance biopsies are superior to functional studies for the diagnosis of acute and chronic renal allograft pathology in children.

In this report of our 3-yr protocol biopsy program, we describe the evolution of acute rejection (AR) and chronic renal allograft nephropathy (CAN) in a cohort of 21 children treated with antibody induction, tacrolimus, mycophenolate mofetil, and prednisone. The aims of this study were to compare the pathogenicity of clinical acute rejection (CAR) and subclinical acute rejection (SAR), and to determine whether functional studies accurately represent acute and chronic renal allograft pathology in pediatric recipients with disproportionately large grafts. Using concurrent biopsies, we evaluated: (i) the utility of changes in the baseline sCr (DeltasCr) to predict both the onset of AR and the response to immunosuppressive therapy; and (ii) the relationship of the calculated creatinine clearance and the presence of pathologic proteinuria to the severity of CAN. We performed 112 biopsies: 11 donor, 73 protocol, 16 acute graft dysfunction and 12 1-month follow-up AR therapy. CAR and SAR were similar in incidence, timing and histologic severity. Progression of CAN was associated with the first episode of CAR (p < 0.02) and the cumulative number of episodes of CAR (p < 0.01), SAR (p < 0.05), CAR plus SAR (p < 0.002) and borderline SAR (B-SAR) (p < 0.006). One-month post-treatment DeltasCrs could not distinguish 1-month follow-up biopsies with histologically confirmed worsened or unchanged AR from those with improved histology (35.2 +/- 74.8% vs. 23.8 +/- 24.9%, p = NS). These findings led to the addition of anti-lymphocyte antibody therapy in five of 10 (50%) cases. Despite 100% 3-yr actuarial graft survival and excellent function (GFR = 111 +/- 36 mL/min/1.73 m(2)), 18 of 21 (86%) patients had grade I CAN or greater chronic histology at a mean +/- sd follow-up period of 18.2 +/- 13.1 months. Thirteen of 21 (62%) patients progressed to grade I CAN at 5.2 +/- 3.6 months and five (38%) of these patients progressed to grade II CAN at 17.8 +/- 11.3 months. Schwartz GFR did not differ between patients with or without CAN (108 +/- 38 mL/min/1.73 m(2) vs. 127 +/- 8 mL/min/1.73 m(2), p = NS). In biopsies with CAN and no associated AR, neither the Banff chronic tubulointerstitial (Banff ci) score nor the Banff chronic grade correlated with the GFR. Proteinuria was not associated with CAN. Clinical AR and SAR are similar histologic lesions with a capacity for CAN progression. In pediatric renal transplant recipients, longitudinal protocol biopsies are superior to functional studies for the diagnosis and post-therapeutic monitoring of AR and for the surveillance of CAN.

Effectiveness and safety of the angiotensin II antagonist irbesartan in children with chronic kidney diseases

Background Studies in adults with chronic kidney diseases demonstrate that the orally available angiotensin II antagonist irbesartan reduces arterial pressure and pathological proteinuria, mostly with an excellent tolerability profile. Little information is available on irbesartan in childhood. Methods A total of 44 pediatric outpatients with chronic kidney disease (27 male and 17, aged 3.7 to 18 years, median 10 years) were given irbesartan once a day during 18 weeks for arterial hypertension ( N = 23), proteinuria ( N = 8), or both ( N = 13). Results In patients with hypertension, the use of irbesartan 4.1 (3.1–5.3) mg/kg body weight daily (median and interquartile range) was associated with a decrease ( P < .005) in arterial pressure by 17 (13–22)/10 (7–12) mm Hg. In patients with overt proteinuria the urinary protein excretion decreased ( P < .01) during treatment with irbesartan (2.9 [2.0–4.8] mg/kg body weight) by 52 (0–75) mg/[m 2 × h]), whereas plasma albumin increased ( P < .05) by 4 (1–5) g/L. The frequency of abdominal pain, constipation, cough, diarrhea, dizziness, edema, fatigue, headache, insomnia, myalgia, orthostasis, and rash was similar before and with irbesartan. Plasma sodium slightly decreased, whereas plasma potassium increased, with irbesartan ( P < .01). Conclusions In pediatric patients with chronic kidney diseases, irbesartan given once a day for 18 weeks significantly reduces arterial pressure and proteinuria, with an excellent tolerability and side effect profile.

Mediation of Systemic Vascular Hyperpermeability in Severe Psoriasis by Circulating Vascular Endothelial Growth Factor

Severe forms of psoriasis can be complicated by systemic microvascular hyperpermeability. Vascular endothelial growth factor (VEGF) possesses potent vascular permeability activity. We suggest that VEGF enters the systemic circulation and acts on microvessels to mediate hyperpermeability. To quantify renal microvascular permeability and circulating VEGF concentration in severe psoriasis, and to investigate the relationship between plasma VEGF concentration and skin and joint involvement. Inception cohort studies of patients with generalized pustular psoriasis and plaque psoriasis. St John's Institute of Dermatology, London, England. Twenty-two patients (15 men and 7 women) with moderate and severe psoriasis were recruited (age range, 29-77 years; mean age, 47 years); 5 had generalized pustular psoriasis, 2 had erythrodermic psoriasis, and 15 had moderate-severe plaque psoriasis. An age- and sex-matched control group of 17 individuals (10 men and 7 women) was recruited (age range, 29-69 years; mean age, 42 years). There was pathological proteinuria in patients with relapsing generalized pustular psoriasis, (4-fold increase in urinary protein excretion rate in relapse compared with remission). In patients with moderate and severe psoriasis, mean plasma VEGF concentration during relapse was approximately 2.5 times greater than during remission (mean VEGF(relapse) = 257 pg/mL; mean VEGF(remission) = 103 pg/mL; P<.01). There was a correlation between extent of skin involvement and plasma VEGF level (mean VEGF(severe psoriasis) = 365 pg/mL; mean VEGF(moderate psoriasis) = 149 pg/mL; P =.03). There was a correlation between presence of psoriatic arthritis and plasma VEGF level (mean relapse VEGF(arthritis) = 277 pg/mL; mean relapse VEGF(nonarthritis) = 103.5 pg/mL; P =.03). Generalized pustular psoriasis is accompanied by pathological proteinuria and elevated plasma VEGF levels. Plasma VEGF concentration is significantly elevated in patients with extensive skin and joint involvement and may act on renal microvasculature to induce hyperpermeability.

Dry chemistry urinalysis of pathological proteinuria.

The paper presents a review of the characteristics and analytical performance of the most current dry chemistry methods for detection and estimation of the different urinary proteins. Description of the classical "protein error" dipsticks for macroalbuminuria is supplemented by data on more sensitive alternatives based on the same principle, reaching into the zone of microalbuminuria. Immunological test strips are available for detection of low concentrations of albumin. Application of the same principle is attempted for detection of other specific proteins. Highly sensitive enzymatic reactions allow detection of "lysis proteins": haemoglobin, leukocyte esterase and beta-N-acetyl-glucosaminidase. An efficient strategy for screening for all types of pathological proteinuria based on detection of low albumin levels is presented.

Renal impairment in patients with long‐standing cyanotic congenital heart disease

Nephropathy is known to occur in patients with long‐standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10–42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular‐type proteinuria in five, with tubular‐type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.

Renal impairment in patients with long-standing cyanotic congenital heart disease.

Nephropathy is known to occur in patients with long-standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular-type proteinuria in five, with tubular-type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.

Hyperviscosity and microproteinuria in central obesity: relevance to cardiovascular risk.

To investigate the role of blood rheology changes in the occurrence of glomerular proteinuria in obese patients with central fat distribution. Fifty-nine obese out-patients (31 with central and 28 with peripheral body fat distribution) and 24 healthy subjects. Blood and plasma viscosity (Rotational viscometer CV100 HAAKE), erythrocyte deformability (whole-blood filtration time), fibrinogen (nephelometry), urinary excretion rates of albumin, IgG, transferrin and IgA (nephelometry). Higher blood viscosity (at low and high shear-rates), plasma viscosity, fibrinogen, erythrocyte aggregability and lower erythrocyte deformability were found in patients with central obesity than in patients with peripheral obesity (P < 0.01) and in healthy subjects (P < 0.001). Furthermore an increased urinary excretion rate of albumin (P < 0.001), IgG (P < 0.001), transferrin (P < 0.01) and IgA (P < 0.05) was found in patients with central obesity than in the other two groups. Blood hyperviscosity (at shear-rate 1 s-1 and 1/200 ratio) significantly correlated with the amount of urinary excretion of proteins independently of the other clinical and metabolic variables. The data demonstrated haemorheologic disorders related to pathologic proteinuria in patients with central obesity. The interaction between these two components may increase the risk of widespread cardiovascular disease.