[Pulmonary complications of sickle cell disease in children]. / Atteintes pulmonaires au cours de la drépanocytose chez l'enfant.

Acute and chronic pulmonary complications are frequent in sickle cell disease (SCD), with different spectrum and characteristics in children and adults. Chronic hypoxia is frequent and plays a role in several respiratory complications in SCD. Furthermore, hypoxia has been associated with a higher risk of cerebral ischemia. Despite differing oxygen affinity between hemoglobin A and S, standard pulse oximetry was shown to be accurate in diagnosing hypoxia in SCD patients. Whereas acute hypoxia management is similar to non-SCD patients, chronic hypoxia treatment is mainly based on a transfusion program rather than long-term oxygen therapy. Acute chest syndrome (ACS) is the foremost reason for admission to the intensive care unit and the leading cause of premature death. Guidelines on its management have recently been published. Asthma appears to be a different comorbidity and may increase the risk of vaso-occlusive crisis, ACS, and early death. Its management is not specific in SCD, but systemic steroids must be used carefully. Pulmonary hypertension (PH) is a major risk factor of death in adult patients. In children, no association between PH and death has been shown. Elevated tricuspid regurgitant velocity was associated with lower performance on the 6-min walk test (6MWT) but its long-term consequences are still unknown. These differences could be due to different pathophysiology mechanisms. Systematic screening is recommended in children. Regarding lung functions, although obstructive syndrome appears to be rare, restrictive pattern prevalence increases with age in SCD patients. Adaptation to physical exercise is altered in SCD children: they have a lower walking distance at the 6MWT than controls and can experience desaturation during effort, but muscular blood flow regulation maintains normal muscular strength. Sleeping disorders are frequent in SCD children, notably Obstructive sleep apnea syndrome (OSAS). Because of the neurological burden of nocturnal hypoxia, OSAS care is primordial and mainly based on adenotonsillectomy, which has been shown to reduce ischemic events. The high morbidity and mortality related to pulmonary impairments in SCD require a careful pulmonary assessment and follow-up. Mainly based on clinical examination, follow-up aims to the diagnosis of SCD-related respiratory complications early in these children.

Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM excretion but not to the changes in the degree of albuminuria.

UNLABELLED: Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM but not to the changes in the degree of albuminuria. BACKGROUND: Albuminuria is believed to correlate to the progression of renal failure in glomerular diseases. Nevertheless, many patients with glomerular disorders maintain their renal function despite persistent albuminuria. In previous studies, we found that the baseline urine excretion of IgM, rather than the degree of albuminuria, predicts the renal outcome in glomerulopathies. In the present study, we examine correlations between changes in the content and in the amount of urine proteins and renal survival during a follow-up time of 3.5 years. METHODS: An observational study of a mean of 44 (+/- 3.6) months was conducted in 37 proteinuric patients (21 males and 16 females) with biopsy-verified primary glomerular disease. The patients were subdivided, according to the findings at the end of the study, into 3 groups, 1 group with decreasing albuminuria (by more than 50%), 1 group with persisting albuminuria and low (< 0.04 mg/mmol creatinine) urinary IgM excretion and 1 group with persisting albuminuria and with high (> or = 0.04 mg/mmol) urinary IgM excretion. RESULTS: All patients that showed remission of albuminuria had also low IgM excretion at the end of the study. All these patients, except 1, maintained their renal function. Patients with persistent albuminuria and high urinary IgM excretion showed a decrease in the glomerular filtration rate (GFR) of a mean of 9.6 ml/min/year compared to a mean GFR increase by 1.5 ml/min/year in patients with low IgM excretion and the same degree of albuminuria (p < 0.01). Seven out of the 9 patients in the former group fall in GFR by more than 5 ml/min/year compared to only 1 of the 10 patients in the latter group. Furthermore, the GFR alterations that occurred during follow-up time correlated in a higher degree to the changes in urinary IgM excretion (r = 0.6, p < 0.01) than to the changes in the degree of albuminuria, (r = 0.4, p < 0.05). A stepwise regression analysis indicated that increased urine IgM excretion is a strong predictor of the GFR decline (r = 0.73, p < 0.001). CONCLUSION: High urinary IgM excretion correlates to decreased GFR in primary glomerular diseases regardless of the degree of albuminuria. In parallel, low urinary IgM excretion indicates beneficial prognosis in these diseases. Since IgM passes the glomerular barrier entirely through large shunts or defects in the glomerular capillary wall, decreased urine content of IgM might be considered as a sign of recovery in the glomerular damage.

Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria.

BACKGROUND: Proteinuric glomerular diseases often are associated with tubulointerstitial injury, which imposes on the progression of renal failure. Tubular damage is partly referable to toxic effects on the tubular epithelial cells induced by filtered plasma proteins. Patients with nonselective proteinuria, that is, increased urine excretion of high-molecular-weight plasma proteins such as IgG in comparison to albumin, often have poor renal outcome. The present observational study examined correlations between the degree of tubular damage, measured by urine concentration of protein HC, and the levels of urine IgG and albuminuria. METHODS: Measurements of urine concentrations of IgG, albumin, and protein HC were performed in 56 proteinuric patients (33 males and 23 females) with nondiabetic glomerular diseases at the time of the diagnostic renal biopsy and at a mean of 49 follow-up months. RESULTS: A highly significant correlation between the urine IgG excretion and the urine protein HC concentration was found both at the start and at the end of the observational time (r = 0.74 and 0.65, respectively, P < 0.001). Furthermore, alterations in the urinary excretion of the two proteins in single patients correlated significantly to each other (r = 0.84, P < 0.001). The correlation between the degree of albuminuria and the protein HC excretion was significant at the time of kidney biopsy, but ceased to exist during the follow-up time. Stepwise linear regression analysis showed that in comparison with the creatinine clearance and albuminuria, only the changes in urinary IgG excretion were related to the corresponding changes in urinary protein HC excretion (r = 0.84 and r2 = 0.7, P < 0.001). CONCLUSION: The findings of the study suggest that the urinary protein HC concentration correlates to the degree of IgG-uria but not to the degree of albuminuria during the course of proteinuric glomerular disease. Whether this correlation is to be explained by an intrinsic toxic effect on tubular cells executed by IgG or perhaps by some other high molecular weight proteins, needs to be investigated further. However, the results contribute to the understanding of the poor renal survival in patients with glomerular diseases and nonselective proteinuria.

Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux--radiological and pathoanatomical analysis.

PURPOSE: To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. MATERIAL AND METHODS: Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. RESULTS AND CONCLUSIONS: The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage.

High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases.

BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.

Conservative treatment and anti-reflux surgery in adults with vesico-ureteral reflux: effect on urinary-tract infections, renal function and loin pain in a long-term follow-up study.

STUDY PURPOSE: To investigate the long-term effects in adults of conservative treatment and anti-reflux surgery for vesico-ureteral reflux on urinary-tract infections, renal function, and loin pain. METHODS: Of 115 adult patients with vesico-ureteral reflux diagnosed between 1968 and 1984, conservative treatment was given to 46 patients (36 women) and anti-reflux surgery was performed in 57 patients (52 women). The remaining 12 patients underwent nephrectomy or heminephrectomy and were excluded from the study. The anti-reflux surgical methods used were the Politano-Leadbetter procedure in 44 patients (73 ureters) and the Hutch procedure in 19 patients (25 ureters). Six of these patients were operated on with both methods. RESULTS: The frequency of acute pyelonephritis was significantly reduced after anti-reflux surgery (P < 0.0001) as well as after diagnosis of vesico-ureteral reflux in the group given conservative treatment (P or < 0.001). The frequency of lower-urinary-tract infections was not altered in either group. Surgery had no effect on significant albuminuria (Albustix > or = 2+) or on progressive renal functional deterioration. Forty-three patients reported recurrent loin pain at the time of diagnosis or anti-reflux surgery. Only one of the 12 patients in the conservative group, compared with 29 of the 31 patients in the anti-reflux surgery group, obtained relief from loin pain during the follow-up. Nine patients in the anti-reflux surgery group reported restitution of reduced general well-being after surgery. These patients had experienced weariness and/or headache before surgery. Vesico-ureteral reflux was eliminated more frequently (P < 0.01) in the patients operated on by the Politano-Leadbetter procedure (94%) than in those operated on by the Hutch procedure (68%). CONCLUSIONS: Loin pain is common in adults with vesico-ureteral reflux and is effectively eliminated by anti-reflux surgery. Anti-reflux surgery should be considered in adults with vesico-ureteral reflux and very frequent acute pyelonephritic attacks only if conservative treatment has failed to alleviate these symptoms. Anti-reflux surgery is not indicated with the aim of arresting renal functional deterioration.

Renal structures in type 2 diabetic patients with elevated albumin excretion rate.

Renal biopsies were obtained from type 2 diabetic patients with elevated albumin excretion. The aim was to obtain quantitative structural data to correlate with clinical findings. Biopsies from 27 diabetic patients and 12 non-diabetic cases were analysed. Stereological methods were applied by light- and electron microscopy. Diabetic patients showed quantitatively markedly expressed diabetic glomerulopathy, but also an increase in glomerular volume, in prevalence of new-vessel formation at the vascular pole, prevalence of glomerular occlusion and in interstitial volume fraction. A significant correlation was not observed between the degree of interstitial and glomerular involvement. The glomerular hypertrophy is interpreted as a compensatory phenomenon, leading to preservation of filtration surface in the open glomeruli. Close correlation was seen between glomerulopathy and glomerular function, and also with the stage of retinopathy. New vessel formation at the vascular pole was most frequent in patients with proliferative retinopathy. Signs of non-diabetic glomerulopathy were not observed, but various atypical ultrastructural changes accompanying the advanced stages are illustrated. Our present findings correspond to data from type I diabetic patients. It is emphasised that all compartments of the kidney are affected by the diabetic state. It is suggested that the interstitial and glomerular lesions are influenced by different factors.

Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases.

The proteinuria selectivity index (SI) describes changes of the glomerular permeability for macromolecules. In the present study, we examine the implications of SI as a diagnostic (199 patients) and a prognostic (49 patients) marker in glomerular diseases. Using SI based on alpha(2)-macroglobulin (alpha(2)-M-SI) or on IgM (IgM-SI) we found that minimal change nephropathy could be discriminated by low SI values and crescentic necrotizing glomerulonephritis by high SI values compared to other diseases. SI based on IgG (IgG-SI) was less useful in determining specific diagnoses. During a follow-up of 46 months creatinine clearance (Cr cl) decreased 36% in a group of patients with high IgG-SI (>0.2) and 38% in a group of patients with high IgM-SI (>1.5(-3)) compared to only 8% in patients with low IgG-SI (

In vivo microvascular clearance of albumin in renal and extrarenal tissues in puromycin aminonucleoside (PAN) induced nephrotic syndrome.

BACKGROUND: The nephrotic syndrome is characterized by generalized oedema considered to be due to the fall in serum albumin and to sodium retention. The aim of the present study was to investigate whether a generalized disturbance in vascular integrity contributes to the oedema formation. METHODS: We used the PAN-(puromycin aminonucleoside) nephritis model in order to induce the nephrotic syndrome in female Wistar rats. Eight rats were given PAN, 15 mg/100 g body weight, intraperitoneally 10 days prior to the study, whereas 21 rats served as controls. Albumin clearance to tissues was measured using a dual isotope technique. Repeated blood samples as well as samples from various muscles, kidney, liver, lung, heart, abdominal wall and from ascites fluid were taken to determine radioactivity and tissue dry-to-wet weights. Clearance of albumin (Clalb) from plasma to interstitium was calculated from the (linear) increment in 'plasma equivalent tissue albumin space' as a function of time, corrected for intravascular volume and oedema. The plasma and urine concentrations of albumin were determined in a parallel study by single radial diffusion using monospecific rabbit anti-rat antiserum in seven PAN animals and 13 controls. RESULTS: A marked fall in dry-to-wet weight ratios together with pronounced proteinuria, oedema and ascites were found in the PAN animals. Haematocrit decreased from 45% (32-51) to 30% (28-38) and serum albumin from 22.0 g/l (16.3-25.2) to 4.94 g/l (3.20-6.72) in control and PAN animals, respectively. However, Clalb apparently remained unchanged in the PAN animals in comparison to controls in most tissues examined. Thus, in these in vivo experiments there was no direct evidence of an increased extravasation of albumin in extrarenal tissues. CONCLUSIONS: There was no strong support for the contention that a generalized disturbance of capillary integrity outside the renal vasculature would contribute to the oedema formation in the PAN nephrotic syndrome.

Urine IgG2/IgG4-ratio indicates the significance of the charge selective properties of the glomerular capillary wall for the macromolecular transport in glomerular diseases.

BACKGROUND: Alterations of the charge-selective properties of the glomerular capillary wall are important constituents of the pathogenesis of many glomerular diseases. Thus, differences in the degree of such changes could be of help in understanding the mechanisms governing the transport of macromolecules across the glomerular capillary wall. METHODS: The ratio between urine concentrations of neutral IgG2 and negatively charged IgG4 (IgG2/IgG4-ratio) was measured in 150 proteinuric patients and 21 healthy controls. The patients were subdivided into seven biopsy verified diagnostic groups. RESULTS: The study revealed decreased IgG2/ IgG4-ratio in membranous glomerulonephritis (0.57) compared to healthy controls (2.09) and to all other diagnosis groups; crescentic necrotizing glomerulonephritis (1.28), diffuse proliferative glomerulonephritis (1.10), IgA nephropathy (1.11), mesangial proliferative glomerulonephritis (1.55), minimal change nephropathy (1.00), and nephrosclerosis secondary to hypertension (1.06). Although not statistically significant, there was a tendency towards lower IgG2/IgG4-ratio values in all the studied glomerular diseases compared to healthy controls. CONCLUSIONS: Since IgG is transported entirely through the large pores of the glomerular basement membrane decreased IgG2/IgG4-ratio implies that this pathway is strongly influenced by the charge-selective properties of the glomerular capillary wall. The conclusion that could be drawn from that is that the large pore radius must be discrete, in the order of 80-90 A, and thus not non-discriminatory to macromolecules as previously thought.

Proteinuria selectivity index based upon alpha 2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases. Technical note.

BACKGROUND: The proteinuria selectivity index (SI) may be used to describe changes of the glomerular permeability for macromolecules in glomerular diseases. Proteins the size of alpha 2-macroglobulin (alpha 2 M) or IgM cannot normally pass the glomerular barrier, whereas IgG can pass through the large pores of glomerular basement membrane. Comparison of the clearance of the three high-molecular-weight proteins to that of albumin may be useful in characterization and diagnosis of different glomerular diseases as well as in understanding of the permeability characteristics of the glomerular filter. METHODS: Three types of SI, each calculated as a ratio of clearance of either IgG, alpha 2M or IgM to that of albumin, were measured in 199 proteinuric patients. The patients were subdivided into eight different biopsy-verified glomerular diseases. RESULTS: Two diagnoses could be clearly distinguished using SI based on alpha 2M (alpha 2 M SI) or IgM (IgM SI). Both alpha 2M SI and IgM SI were significantly lower in minimal change nephropathy and higher in crescentic necrotizing glomerulonephritis than in all the other diagnoses. The SI based on IgG (IgG SI) was less useful in determining specific diagnoses, since patients with minimal change nephropathy could not be distinguished from those with other types of primary glomerulonephritis and patients with crescentic necrotizing glomerulonephritis did not differ from those with diabetic nephropathy. CONCLUSIONS: The findings of this study indicate that alpha 2M SI and IgM SI are superior to IgG SI in characterization of glomerular disorders and might replace the IgG SI for this purpose.

Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways.

To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins into the primary urine. This protein excretion pattern was almost the same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the number of large and small pores was calculated to be approximately equal to 7 x 10(-7) in normal rats and to 1.2 x 10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existed, they would normally contribute to no more than approximately equal to 10(-5) of the total glomerular filtration rate. We postulate that very large macromolecules like IgM will not pass the glomerular filter at all under normal conditions, whereas the urine concentration of alpha2-macroglobulin will normally be extremely low.

Decreased excretion of glycosaminoglycans in patients with primary glomerular diseases.

Urine glycosaminoglycans (GAG) concentrations were measured in 150 patients with primary glomerulonephritides: endocapillary glomerulonephritis, mesangial proliferative glomerulonephritis, IgA nephropathy, membranous glomerulonephritis and minimal change nephropathy, and in 63 healthy controls and 19 patients with diabetes nephropathy. The urine GAG to creatinine ratios (GCR) were significantly reduced (p < 0.01) in all the glomerulonephritides investigated (0.20 mg/mmol in endocapillary glomerulonephritis, 1.60 mg/mmol in mesangial proliferative glomerulonephritis, 1.74 mg/mmol in IgA nephropathy, 1.09 mg/mmol in membranous nephropathy, and 1.16 mg/mmol in minimal change nephropathy) compared to healthy controls (2.87 mg/mmol) but not compared to diabetes patients (1.17 mg/mmol). Also, the GCR in a group of 23 non-albuminuric glomerulonephritis patients (1.98 mg/mmol) was shown to be significantly decreased (p < 0.01) compared to healthy controls. Moreover, the GCR was significantly lower (p < 0.01) in endocapillary glomerulonephritis than in any of the other diseases studied. The GAG excretion per functioning glomerular area, calculated as fractional GAG excretion (FGE), was decreased in all the glomerulonephritides investigated compared to both healthy controls and diabetes nephropathy. The decreased GAG excretion in glomerulonephritides, obtained in the present study, might be a consequence of decreased synthesis or turnover of GAG in the functioning nephrons whereas the mechanisms for the reduced GAG excretion in diabetes nephropathy might be of a different nature. Urinary GAG excretion in this group of glomerular disorders and particularly in endocapillary glomerulonephritis, may lead to new approaches in non-invasive renal diagnostics and, particularly with regard to the differentiation of acute and chronic forms of glomerulonephritides.

Decreased excretion of urine glycosaminoglycans as marker in renal amyloidosis.

BACKGROUND: The diagnosis of renal amyloidosis is normally established by kidney biopsy. In order to advance the determination of the diagnosis and the initiation of the therapy, fast and cheap, non-invasive diagnostic techniques are required. METHODS: Urine excretion of glycosaminoglycans (GAG) was measured in 10 patients with AA amyloidosis and 5 patients with AL amyloidosis and compared to 25 controls with primary glomerular diseases and 22 healthy controls. The subjects with primary glomerular disease were matched with regard to their renal function and the degree of albuminuria. RESULTS: The median urine GAG to creatinine ratio and the median fractional GAG excretion were significantly decreased (P < 0.05) in both AA amyloidosis (0.21 mg/mmol and 0.053 respectively) and AL amyloidosis (0.33 mg/mmol and 0.077 respectively) compared to control patients with primary glomerular disease (1.73 mg/mmol and 0.336 respectively) and healthy controls (2.67 mg/mmol and 0.226 respectively). The urine GAG to creatinine ratio did not correlate to age, sex, serum creatinine, urine albumin, or to the plasma levels of acute phase proteins. CONCLUSIONS: The decreased GAG excretion in renal amyloidosis is probably caused both by diminished number of functioning nephrons, decreased GAG synthesis in functioning glomeruli, and the trapping of GAG by amyloid fibrils. Urinary GAG excretion may serve as an independent marker of renal amyloidosis. It may be used in diagnostic work-up of renal amyloidosis in patients with glomerular diseases and in screening of amyloidosis in patients with chronic inflammatory disorders, with or without signs of renal disease.

Long-term stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain-immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at -20 degrees C.

The stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at -20 degrees C for up to 24 months was investigated. Significant decreases of the median concentration values for protein HC, IgG and alpha 1-antitrypsin were observed for native urine. Addition to urine of a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide prevented the decreases of the concentration values for protein HC and IgG but not for alpha 1-antitrypsin. The median concentration values for albumin, orosomucoid and kappa- and lambda-chain immunoreactivity did not change significantly upon storage of native urine, nor for urine with the preservative solution.

Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi.

STUDY PURPOSE: To determine the incidence of urinary tract infections, hypertension, back pain, and renal calculi in adult patients with vesicoureteral reflux and reflux nephropathy. METHODS: A group of 115 patients (16-60 years of age, median 28 years) with vesicoureteral reflux, combined with reflux nephropathy in 101 patients, first detected between 1967 and 1984, was studied retrospectively. The group comprised 99 women and 16 men. RESULTS: Symptoms and findings associated with the urinary tract preceded the diagnosis of vesicoureteral reflux by median 14 years (1-60 years). Intravenous pyelography preceded investigation with micturating cystography in 99 patients. Fifteen patients had no urinary tract infections, 17 patients had only lower urinary tract infections, and 83 patients had upper with or without lower urinary tract infections. Females had 12 times more lower and seven times more upper urinary tract infections than males, whereas males had impairment of renal function and proteinuria more often than females. Hypertension was present in 39 patients (34%) and five times more frequent in patients with bilateral than in those with unilateral reflux nephropathy. The median age at the first recording of hypertension was 33 years (16-60 years). Malignant hypertension was uncommon and occurred in two patients. An older group (> 45 years of age at presentation) of 19 patients showed a 90% incidence of hypertension compared with 23% in 96 patients in the younger group (< or = 45 years of age at presentation). Back pain of varying type and severity was present in 48 patients (42%). A total of 38 renal calculi was found in 21 (18%) patients, of whom 14 were completely asymptomatic. CONCLUSIONS: The natural history of vesicoureteral reflux first detected in adulthood has shown a strikingly high incidence of urinary tract infections, arterial hypertension, back pain, and renal calculi.

Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin.

Efficient use of assessment of urine protein excretion in nephrological practice requires adequate reference intervals. To determine the upper reference limits of urine albumin, protein HC (alpha 1-microglobulin, immunoglobulin G (IgG), orosomucoid (alpha 1-acid glycoprotein, alpha 1-antitrypsin, and kappa- and lambda-chain immunoreactivities, the concentrations of these proteins were measured in urine samples from 95 healthy, adult individuals, using rapid, generally available methods and with conditions for urine collection which secured stable protein levels. The obtained values were expressed in mg 1(-1), as the urine protein-creatinine index and as fractional protein-creatinine clearance. No differences were found between the upper reference limits in the first voided morning urine samples and the randomly collected urine samples, nor between the upper reference limits in urine samples collected from males and females. The urinary excretion of the tested proteins did not correlate to age, positive dipsticks for haematuria nor to granular casts in urine sediment. Thus, the same upper reference limits can be used for both sexes and regardless of the type of urine collection. The upper reference limits of urine protein-creatinine index found in this study were: for albumin, 3.8 mg mmol(-1); for protein HC, 0.7 mg mmol; for IgG, 0.8 mg mmol(-1); for orosomucoid, 0.7 mg mmol(-1); for alpha 1-antitrypsin, 0.2 mg mmol(-1), and for kappa-immunoreactivity 0.7 mg mmol(-1). The upper reference limit for lambda-immunoreactivity was below the detection limit.

Elevated plasma levels of acute phase proteins in mesangioproliferative glomerulonephritis, membranous nephropathy and IgA nephropathy.

In order to study the possible role of active inflammatory processes in clinical indolent primary chronic glomerulonephritides, plasma concentrations of the acute phase proteins: alpha 1-antitrypsin, haptoglobin, orosomucoid and C-reactive protein were measured in 166 glomerulonephritis patients. The patients had a diagnosis of either mesangioproliferative glomerulonephritis, membranous nephropathy or immunoglobulin A nephropathy and were divided in two groups, one with heavy urinary albumin losses and one with moderate to slight urinary albumin excretion. The median plasma concentration values for alpha 1-antitrypsin, haptoglobin and orosomucoid were increased in all three kinds of the investigated glomerulonephritides with exception for orosomucoid in patients with heavy urinary albumin losses and in the membranous nephropathy group. The plasma concentration values for C-reactive protein were not elevated at all in the material. The increase of plasma levels of acute phase proteins could be the result of persistent inflammatory stimuli that occur in primary chronic glomerulonephritides. The finding of unchanging plasma levels of C-reactive protein in contrast to increased concentrations of the other acute phase proteins could be of significance in diagnosing infections or other inflammatory diseases in patients with chronic glomerulonephritis.

Stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at various conditions.

Urine samples from 10 randomly selected patients with advanced renal disease were each divided into six aliquots and a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide was then added to three of the aliquots. Aliquots with and without additive were then stored at room temperature for up to 7 days, at 4 degrees C for up to 30 days and at -20 degrees C for up to 6 months. The concentrations of albumin, protein HC, IgG, orosomucoid and alpha 1-antitrypsin as well as the kappa- and lambda-chain immunoreactivities in the samples were determined by automated immunoturbidimetry or by single radial immunodiffusion after 1, 3, 7, 14, 30, 90 and 180 days of storage. All investigated proteins, except alpha 1-antitrypsin in native urine, were stable for 7 days in the samples stored at room temperature both in the presence and absence of additives. All investigated proteins, except alpha 1-antitrypsin in native urine, were stable for 30 days in the samples stored at 4 degrees C both in the presence and absence of additives. A more complex pattern was observed for the stability of the proteins in the frozen samples. The IgG level decreased rapidly in several samples stored without additives but not in samples stored with additives. The alpha 1-antitrypsin concentration decreased rapidly to about 50% of the initial value in several samples stored both with and without additives. The rate of the decrease for both the IgG and the alpha 1-antitrypsin level varied between samples and the main decrease for several samples was seemingly caused by the freezing and/or thawing per se and not by the storage period in between.