Long-standing changes in the urinary profile of porphyrin isomers after clinical remission of porphyria cutanea tarda

Patients with overt porphyria cutanea tarda (PCT) show a distinctive and abnormal urinary profile of porphyrin excretion. It is not known, however, whether clinical remission of the disease produces complete normalization of this profile. We selected 46 patients, previously diagnosed with PCT, who after treatment presented normal levels of total porphyrins in urine (< 35 nmol/mmol creatinine). We analyzed their urine specimens by hplc to identify and quantify the various porphyrins and we compared the urinary porphyrin profiles to those of 40 healthy volunteers. While healthy volunteers gave a pattern dominated by excretion of coproporphyrin III, 80% of the PCT patients in clinical remission showed the characteristic profile of PCT, with decreased coproporphyrin-to-uroporphyrin ratio and/or inversion of the normal coproporphyrin III-to-coproporphyrin I ratio. Detection of uroporphyrin III and heptacarboxyl III intermediates was significantly more common among the patients than the controls (p < 0.05). This study shows that PCT patients demonstrate persistent changes in urinary porphyrin profiles during clinical remission, even when total urinary porphyrin excretion has fallen to the normal range.     

Determination of renal porphyrin handling in rats suffering from different kinds of chronic renal failure (CRF): Uranyl nitrate (UN) induced fibrosis or 5/6-nephrectomy (5/6NX)

The renal handling of porphyrins is reported to be a sensitive marker for chronic renal failure (CRF) for two reasons: heme is synthesised in proximal tubules and porphyrins are reabsorbed in the renal proximal tubule by apical peptide transporter PEPT 2. Two different models of CRF in female Wistar rats have been used for investigation of renal porphyrin handling: (1) single administration of uranyl nitrate (UN; 0.5 mg/100 g b.wt.) and (2) 5/6 nephrectomy (5/6NX). Renal clearance experiments were performed at weeks 2 and 10 after the onset of CRF. The concentrations of porphyrin intermediates (uroporphyrin I and III, coproporphyrin I and III, heptaporphyrin, and pentaporphyrin) were measured by HPLC with fluorescence detection.

Both after UN and 5/6NX a significant reduction of body weight occurred. The kidney weight was enhanced 2 weeks after UN compared to controls (+31%). After 5/6NX, the weight of the remnant kidney was 44% (2^nd week) and 140% (10^th week) higher compared to one control kidney.

Urine volumes and GFR were significantly reduced at week 2 and 10 after 5/6NX, but at week 10 after UN values were comparable to controls.

Two weeks after UN and 5/6NX the concentrations of heptaporphyrin was moderately decreased in renal tissue whereas after 10 weeks the concentrations of most porphyrins were increased in the kidney. The plasma levels of free porphyrins were only slightly enhanced (week 2). The renal excretion of porphyrins was initially slightly reduced in both models, whereas it increases 10 weeks after UN, but it remained reduced 10 weeks after 5/6NX.

UN induces tubulointerstitial fibrosis including atrophic glomeruli, whereas 5/6NX was characterized by distinct proteinuria, dilated tubules containing hyaline casts. A modulation of porphyrin metabolism in the kidney seems first of all to be responsible for UN effect on renal porphyrin handling. Summing up the 5/6NX results, both reduction in intact renal tissue mass and a modification of enzymes involved in heme biosynthesis by uraemic toxins are responsible for accumulation of porphyrins in renal tissue. After 5/6NX reduced excretion of porphyrins into urine and enhanced porphyrin concentrations in the kidney indicate more a damage of renal porphyrin biosynthesis than changes in their reabsorption.     

Urinary porphyrin patterns in hepatic porphyrias

Summary The characteristic patterns of distribution of the urinary porphyrins with eight to four carboxyl groups are of relevance in the diagnosis of hereditary and acquired forms of hepatic porphyria. Whereas the excretion types in acute intermittent and in variegate porphyria both show alternating predominance of uro- and coproporphyrin, in hereditary coproporphyria coproporphyrin can be the only extremely elevated component. A gradual, moderate to excessive increase of uroand heptacarboxylic porphyrin characterizes the acquired, asymptomatic chronic hepatic porphyrias up to and including porphyria cutanea tarda.     

Biochemical and genetic characterization of four cases of hereditary coproporphyria in Spain

We report a biochemical and genetic characterization of four cases of hereditary coproporphyria (HCP) in Spain. All patients showed a typical HCP porphyrin excretion pattern with a high concentration of coproporphyrins in feces and inverted I:III isomer ratio. The porphyrin precursors in urine were found elevated in two patients who showed acute symptoms. The analysis of the CPO gene showed that three cases harboured novel mutations: V135A (404T>C; exon 1); L214R (641T>G; exon 2); and P249R (746C>G; exon 3) and in the fourth, a previously described R426X mutation in exon 6.     

Hepatic porphyrins and urinary prophyrins and prophyrin precursors in liver cirrhosis

Summary In 21 liver cirrhotics (19 men, 2 women) the urinary excretion of-aminolevulinic acid, porphobilinogen, uro- and coproporphyrin, and hepta-, hexa-, and pentacarboxylic porphyrin was studied. Porphyrins in liver biopsy tissue were also analyzed in 17 of the 21 cases. Only a single patient had slight clinical symptoms of porphyria cutanea tarda.Porphyrin excretion was normal in six of the patients, and six showed moderate to severe coproporphyrinuria. Excretion of-aminolevulinic acid and porphobilinogen was normal in all cases. Under 366 nm UV light the liver tissue from three patients, including the one with porphyria cutanea tarda, exhibited the red fluorescence characteristic of porphyrin. On the basis of the constellation of urinary porphyrins and the storage of uro- and heptacarboxylic porphyrin in the liver, chronic hepatic porphyria Type A was diagnosed in two patients, and chronic hepatic porphyria Type B, Type C, and porphyria cutanea tarda in one patient each. In eight of the fourteen non-red-fluorescent hepatic tissue specimens the content of uroporphyrin, and in some of these cases of heptacarboxylic porphyrin as well, was usually slightly elevated, as observed both in four patients with normal and in four with abnormal coproporphyrin excretion. The increased levels of porphyrin in three patients were possibly due to certain drugs, the porphyrinogenic effect of which is known from experiments.The present study includes all stages of biochemical manifestation of chronic disturbance of hepatic porphyrin synthesis, i.e., four patients with clinically inapparent chronic hepatic porphyria.Types A, B, and C, in the order of degree of porphyrin accumulation in the liver and the order in which the individual urinary porphyrins increase. This supports the contention that hepatic cirrhosis in itself provides the conditions triggering the development of chronic hepatic porphyria. Induction of-aminolevulinic acid synthase by sexual hormones and their metabolites due to impaired steroid conjugation may be one factor in the pathogenesis, which is of complex nature; just why liver cirrhosis should produce secondary coproporphyrinuria in some cases and chronic hepatic porphyria and porphyria cutanea tarda in others still remains an open question.No correlation was found between the concentrations of porphyrins in liver and urine and clinical-chemical data from serum analysis and the bromosulfophthalein test.     

Persistent protoporphyrinemia in hereditary porphobilinogen synthase (δ-aminolevulinic acid dehydrase) deficiency under low lead exposure

Summary For several years, a 4–12-fold increase of the upper normal limit in erythrocyte protoporphyrin concentrations persisted in two men 34 and 39 years of age who were chronically exposed to lead. We are dealing with a zinc protoporphyrinemia in both cases, without lead intoxication or anemia. The 34-year-old had been a regular blood donor for 10 years and had already been treated for iron deficiency several times. Hemoglobin, red cell counts, hematocrit, and iron were at the lower normal limit. The activity of porphobilinogen synthase (PBG-S), uroporphyrinogen-synthase and -decarboxylase as well as urinary porphyrin precursors and porphyrin excretion were normal. Protoporphyrinemia was said to be due to a prelatent/latent iron deficiency.In the 39-year-old, the activity of PBG-S was lowered to 388 µmol/l·h, as compared to the mean of controls (1,190±210,x±SD,n=50), in connection with a slightly elevated excretion of -aminolevulinic acid and coproporphyrin in the urine and a high-normal blood lead level. In his family there was no history of either a protoporphyrinemia or a hematological disturbance. Six of eight family members in three generations showed a diminished activity of PBG-S: 600±160,P<0.001 compared to controls. These family members are heterozygous with regard to the PBG-S deficiency; they are clinically unobtrusive in comparison to homozygotes with an acute prophyria syndrome. Activation by zinc and reactivation by dithiothreitol were normal in contrast to PBG-S from patients with lead intoxication. The cause of biochemical symptoms of subclinical lead intoxication developed by the propositus is probably due to the hereditary PBG-S deficiency which sensitizes him to low-level lead exposure. The determination of red cell PBG-S activity can be recommended as a test detecting heterozygotes.The hereditary PBG-S deficiency is recognized as a new molecular basis for the pathogenesis of lead intoxication.This work is dedicated to Prof. Dr. Rudolf Gross on the occasion of his 65th birthday     

Autosomal dominant Fanconi syndrome with early renal failure

The “idiopathic” Fanconi syndrome occurs mostly sporadically, occasionally as an autosomal recessive trait. However, few instances of autosomal dominant inheritance have been reported. We described a father and son with the Fanconi syndrome, ie, with renal glycosuria, generalized aminoaciduria, phosphaturia, metabolic acidosis, and bone disease. No other causes of the Fanconi syndrome were found. Both father and son developed end stage renal disease. Aminoaciduria in excess of that seen in renal insufficiency is shown by comparison with published data for amino acid excretion in uremia. Renal transplantation in the father has improved kidney function with no evidence of Fanconi syndrome. This family is unique in that there are no other reports of autosomal dominant Fanconi syndrome with progression to early renal failure.     

Autosomal dominant Fanconi syndrome with early renal failure.

The "idiopathic" Fanconi syndrome occurs mostly sporadically, occasionally as an autosomal recessive trait. However, few instances of autosomal dominant inheritance have been reported. We described a father and son with the Fanconi syndrome, ie, with renal glycosuria, generalized aminoaciduria, phosphaturia, metabolic acidosis, and bone disease. No other causes of the Fanconi syndrome were found. Both father and son developed end stage renal disease. Aminoaciduria in excess of that seen in renal insufficiency is shown by comparison with published data for amino acid excretion in uremia. Renal transplantation in the father has improved kidney function with no evidence of Fanconi syndrome. This family is unique in that there are no other reports of autosomal dominant Fanconi syndrome with progression to early renal failure.     

Bile porphyrin analysis in the evaluation of variegate porphyria

BACKGROUND: Variegate porphyria is a genetic disorder of porphyrin metabolism in which patients may have both neurologic dysfunction and photocutaneous lesions. Biochemical confirmation of the diagnosis can be difficult, particularly in patients without neurologic dysfunction at the time of testing. The demonstration of increased fecal excretion of porphyrin is frequently used for this purpose, but levels may be normal. Since elevated fecal porphyrin levels in variegate porphyria are presumably a consequence of increased biliary excretion, we evaluated whether analysis of porphyrins in bile distinguishes better between patients with variegate porphyria and controls. METHODS: Bile samples were collected by duodenal aspiration from 10 patients with proved variegate porphyria who had no neurologic symptoms when they were studied and 17 control subjects. Bile and fecal porphyrin levels were measured fluorometrically. RESULTS: The mean total porphyrin concentration in bile in the patients with variegate porphyria was significantly higher than that in the controls (67.8 vs. 0.71 mumol per liter; P less than 0.00002). There was more than a ninefold difference between the highest level in any control subject and the lowest level in any patient with variegate porphyria. The mean fecal porphyrin level in the patients with variegate porphyria also differed significantly from that in the controls (0.79 vs. 0.14 mumol per gram of dry weight; P less than 0.007), but four patients had levels within the control range. CONCLUSIONS: The concentration of porphyrin in bile is higher in patients with variegate porphyria than in controls, and the difference is greater than that for fecal porphyrin. Bile porphyrin measurements may be helpful in the evaluation of asymptomatic patients suspected of having variegate porphyria.     

Primärer Hypoaldosteronismus und sekundärer Pseudo-Hypoaldosteronismus

Summary We observed a 23-year-old man with pronounced hyperkalemia (max. 6.8 mmol/l) and hyponatremia (min. 112 mmol/l), which had been existent for 3 years without complaint except a transitory psychorganic syndrome due to hyponatremia. Physical examination showed no abnormality except hypotension (blood pressure 100/70 mmHg). Renal function tests were normal. Fractional clearance of sodium was significantly increased (0.8%), whereas that of potassium was decreased (2.4%). Plasma renin activity was tripled and rose after furosemide. Plasma aldosterone was lowered and showed no rise after furosemide. Suppression of plasma renin and aldosterone by saline infusion was normal. Pressor dose of angiotensin II was increasend (17,9 ng AT II/kg/min). Urinary excretion of aldosterone and its conjugates was below normal, and aldosterone precursors were within normal range. The findings were interpreted as selective primary hypoaldosteronism caused by corticosterone methyl oxidase defect type II. However, neither fludrocortisone (0.5 mg/day) nor sodium chloride (200 mmol/day) led to a normalization of sodium and potassium in plasma. Additional pseudohypoaldosteronism was thus assumed. Aldosterone infusion (3 mg in 1 h) decreased renal excretion of sodium; potassium excretion failed, however, to increase in contrast to its pattern in normal man. These findings resemble additional pseudohypo-aldosteronism of type II. After 8 weeks' application of additional 80 mmol sodium (as sodium bicarbonate) plasma sodium and potassium showed normal values under combined treatment with fludrocortisone (0.1 mg/day) and sodium bicarbonate (80 mmol/day). It is to be assumed that the patient suffers from a reduced aldosterone biosynthesis in the presence of an additional transitory secondary pseudohypoaldosteronism.

     

Änderungen der renalen Eiweißausscheidung und der Nierenfunktion bei Typ I Diabetikerinnen während und nach einer Gravidität in Abhängigkeit vom Stadium einer präexistenten diabetischen Nephropathie

Summary In 14 female type I diabetics the influence of preexisting diabetic nephropathy on the behaviour of proteinuria and renal function during and after pregnancy was investigated. We compared albumin and total protein in urine, serum-creatinine, creatinine-clearance, uric acid and beta₂-microglobuline in serum before, during and up to sixth months after pregnancy in 5 diabetic women with preexisting normoalbuminuria, stage II of diabetic nephropathy, in 6 women with microalbuminuria, stage III, and in 3 women with overt proteinuria, stage IV of diabetic nephropathy (by Mogensen); in this last patient-group there was a heavy proteinuria with decreased creatinine clearance and high blood pressure still before the begin of the pregnancy.The albumin- and total protein excretion in urine showed in all diabetic patients a 3- to 8-fold increase during pregnancy and in all cases the increased proteinuria dropped after pregnancy to the preexisting values. A transient nephrotic syndrome in pregnancy developed in 2/6 diabetic women with primary microalbuminuria and in all 3 patients with overt proteinuria, but not in any case of pregnant women with primary normoalbuminuria; the difference between the absolute increase of proteinuria in the 2 patient-groups with stage II and III of diabetic nephropathy was statistically significant (p<0,005).The renal function parameters serum-creatinine and creatinine-clearance showed in all pregnant women with stage II or III of diabetic nephropathy the same transient changes as in non-diabetic pregnant women, the mean serum-creatinine concentration showed a decline of 36% respectively 14%, the creatinine clearance an increase of 31% and 36%. The serum uric acid concentration increased during pregnancy also in the same way as in non-diabetics, beta₂-microglobuline in serum did not change significantly during and after pregnancy and is therefore no good parameter for GFR in pregnant women. In the diabetic women with pre-existing overt proteinuria and still reduced creatinine-clearance there was a further increase of serum-creatinine and decline of creatinine-clearance during pregnancy. This progredient decline of renal function also during pregnancy can be explained with the increased blood pressure in this patient-group, despite of intensified treatment of hypertension the blood pressure could not be normalized. Uric acid and beta₂-microglobuline in serum showed the same increase during and after pregnancy in these patients according to the decrease of GFR.

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Abkürzungsverzeichnis GFR glomeruläre Filtrationsrate - HbA1c glukosyliertes Hämoglobin - RIA Radioimmunoassay     

Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria

Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.     

Unterschiedliche Werte von Lipoprotein Lp(a) bei erwachsenen Diabetikern in Abhängigkeit von der Therapieform

Summary A total of 60 newly admitted hospital patients with maturity onset diabetes mellitus and normal kidney function were studied. They were either treated only with a diet (group I), or also with blood-sugar lowering sulfonylureas (group II). Some patients had become insulin-dependent (group III). It was found that the mean serum concentration of lipoprotein Lp(a) was significantly increased in patients in groups II and III, but not in group I, as compared to the median of the group of 51 normal controls. All three groups of diabetics showed normal LDL cholesterol levels but lowered HDL cholesterol values, most pronouncedly in group II. Groups I and II, but not group III, showed a significant increase of the mean serum concentration of triglycerides and of the mean values for the LDL/HDL ratio as compared to normal controls. A correlation between the serum concentration of Lp(a) on the one hand, and the HbA₁ value, LDL cholesterol, VLDL, HDL cholesterol, phospholipids, triglycerides and total cholesterol on the other, cannot be found for any of the three groups of diabetics.

     

Der mikrofluorescenzoptische Nachweis von Porphyrinen in der Leberbiopsie

Zusammenfassung Mittels mikrofluorescenzoptischer Untersuchung gelang es in frisch hergestellten Zupfpräparaten einer Leberbiopsie bei 4 Patienten Porphyrine nachzuweisen ohne daß eine erhöhte Uro- und/oder Koproporphyrinurie bzw. Hauterscheinungen zu beobachten waren. Die Bedeutung dieser einfachen Methode für die Frühdiagnose einer Porphyrinstoffwechselstörung wird dargelegt.

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Summary Red fluorescence of porphyrins was found in freshly specially prepared liver biopsies (Zupf-preparation) by microscopic investigation in 4 patients. In these patients an increased uro- and/or coproporphyrin excretion in the urine, skin lesions or any other manifestation of porphyria were not demonstrable. The diagnostic value of this simple method for early detection of disorders of the porphyrin metabolism is discussed.

     

Clinical, morphological and biochemical features in the familial articular hypermobility syndrome (FAHS): a family study

A female with clinical features of familial articular hypermobility syndrome (FAHS) and her family were studied. The subject showed generalized hypermobility, except for a painful shoulder which presented functional limitation with a diagnosis of painful shoulder syndrome. Biochemical studies demonstrated that collagen and glycosaminoglycans (GAGs) contents from skin biopsies of the subject and her family were almost normal. Nevertheless, the densitometric analysis of electrophoretic patterns showed differences in the relative proportions of their collagenous components. They were characterized by changes in type I and III collagens and the presence of type V collagen, in the subject, her father and brother. Also, they presented changes in the types of GAGs, when compared with those of normal skin. Morphological studies revealed a general disorganization of dermal components, a loose collagen network characterized by thick bundles. Also, besides cellular elements, the presence of an abundant darkly staining material was observed.
Biochemical and morphological findings permit us to suggest a connective tissue defect, initially described in the FAHS, otherwise known as Ehlers-Danlos syndrome (EDS) type XI.     

The synergistic effect of chlorinated chemicals (trichlorosalicylanilid, 4-chloro-m-cresol, trichlorophenoxyacetic acid, trichloroethanol, trichloromethiazide, trichlorofon and trichloroacetaldehyde) and low concentrations of griseofulvin on porphyrin metabolism

The synergistic effect of chlorinated chemicals and 0.1% griseofulvin (GF) on porphyrin metabolism was investigated. Drinking water containing 0.03% trichlorosalicylanilid, 0.1% 4-chloro-m-cresol, 0.1% trichlorophenoxyacetic acid, 0.3% trichloroethanol, 0.1% trichloromethiazide, 0.3% trichlorofon and 0.1% trichloroacetaldehyde was given separately to dd-y strain mice. Each group was divided into two subgroups, one treated with feed containing 0.1% GF and the other treated with normal feed. The treatments were continued for 45 to 165 days, after which porphyrins in the erythrocytes, feces and liver were analyzed by a chromatographic method. In the 0.03% trichlorosalicylanilid and 0.1% GF group, 0.1% 4-chloro-m-cresol and 0.1% GF group, 0.1% trichlorophenoxyacetic acid and 0.1% GF group and 0.3% trichloroethanol and 0.1% GF group, a slight elevation of fecal coproporphyrin and protoporphyrin was seen. There was no elevation of hepatic and erythrocytic porphyrins. This result shows that the chemicals used in this study did not have a potential for porphyria, but that they are capable of inducing slight porphyrin abnormalities in a synergistic reaction with 0.1% GF.     

Die sympathische Aktivität bei terminaler Niereninsuffizienz und Nierentransplantation

Summary Blood pressure as well as noradrenaline, creatinine and electrolytes in blood and urine were compared in normal controls (n=25), patients with chronic renal failure (n=39), patients with continuous ambulatory peritoneal dialysis (CAPD) (n=28) and haemodialysis patients before and after renal transplantation (n=63). The average blood pressures of the control group and the CAPD patients were lower than those of the renal failure patients without and with haemodialysis. After renal transplantation elevated blood pressure normalised in 18% within the following 6 months. In all groups of patients with renal failure the mean noradrenaline plasma concentration was increased more than three-fold of normal values: 1,470 pg/ml in patients with chronic renal failure, 1,366 pg/ml in CAPD patients and 1,284 pg/ml in patients with haemodialysis. No correlation was found between these elevated noradrenaline plasma levels and blood pressure. However, there was a significant correlation between noradrenaline excretion and sodium excretion. Compared to the controls, the urine excretion of noradrenaline was significantly lower in patients with chronic renal failure and almost zero in patients with dialysis treatment. Two days after renal transplantation the mean noradrenaline urine excretion increased to 15.7±1.8 µg/day and 4 days after transplantation the noradrenaline plasma concentration decreased to 592±155 pg/ml. Nine months after renal transplantation the creatinine clearance was 76 ml/min and the mean noradrenaline plasma concentration 438±153 pg/ml. It is concluded that in chronic renal failure the level of noradrenaline plasma concentration is dependant on renal function.

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Abkürzungen CAPD continuous ambulatory peritoneal dialysis Zum 60. Geburtstag von Herrn Prof. Dr. W. Kaufmann     

Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasia

We report what we believe to be the first case of a patient with multiple endocrine neoplasia type 2A (MEN 2A) and renal dysplasia associated with an RET 634 mutation. The proband presented at the age of 29 with medullary thyroid carcinoma (MTC), bilateral pheochromocytomas, and primary hyperparathyroidism. Screening of family members identified the syndrome in his father. Both the proband and his father carry RET 634 germline mutation resulting in cysteine to arginine amino acid substitution. The proband had a left nephrectomy at the age of 10 years. Histologic examination of the resected kidney revealed severe dysplasia. His father had normal renal tract on ultrasonography. The proband's clinical presentation was unusual, and initially thought to be an atypical pneumonia. Surgical management after pharmacologic alpha- and beta-blockage consisted of bilateral adrenalectomy, total thyroidectomy, and subtotal parathyroidectomy as a single procedure.     

Interrelationships between sodium clearance,plasma aldosterone,plasma renin activity,renal hemodynamics and blood pressure in renal disease

Summary This study was designed to evaluate the role of aldosterone, glomerular filtration and blood pressure on sodium excretion in renal disease. Sodium clearance (C_Na), plasma aldosterone (PA), plasma renin activity (PRA), glomerular filtration rate (GF), paraaminohippurate clearance (C_PAH) and blood pressure were measured simultaneously in 19 normal subjects, 38 patients with benign essential hypertension, 3 with renal artery stenosis, 48 with chronic glomerulonephritis, 20 with the nephrotic syndrome, 24 with tubulo-interstitial disease and 21 with a renal homograft.C_Na was significantly depressed in patients with the nephrotic syndrome. Mean PA and PRA were increased in renal artery stenosis, but within the normal range in the other groups. C_Na correlated inversely with PA in all groups but one (tubulo-interstitial disease). C_Na correlated directly with GF in the nephrotic syndrome and with the mean blood pressure (mBP) in chronic glomerulonephritis and tubulointerstitial disease. PA correlated directly with PRA and inversely with GF or C_PAH in most groups.It is concluded that PA is an important determinant of the basal natriuresis in renal disease with the exception of tubulo-interstitial nephropathies. In the nephrotic syndrome sodium retention is largely determined by the interaction of PA and GF. In chronic nephropathies, but not in benign essential hypertension, the fractional sodium excretion is partly blood pressure-dependent. Impairment of renal function is often accompanied by a rise in PA.     

Homozygous variegate porphyria A severe skin disease of Infancy

A boy exhibited severe bullous skin disease a few days after birth, followed by increased fragility of the exposed skin in spring and summer. Examination at 2 1/2 years of age led to characteristic biochemical findings: increased excretion of fecal porphyrins (coproporphyrin 121 to 131 and protoporphyrin 467 to 576 nmol/g dry weight), and increased erythrocyte protoporphyrin concentration (3643 to 4840 nmol/I). Lymphocyte protoporphyrinogen oxidase activity was very low in the patient (0.4 nmol/mg protein/h) and half-normal (2.7 and 2.3 nmol/mg protein/h) in the parents, suggesting that the patient had homozygous variegate porphyria. Severe skin symptoms and a high concentration of red cell protoporphyrin concentration in an infant should prompt suspicion of homozygous acute hepatic porphyria.