PubMed Health⌕ Search

Biomedical subjects

R Waldherr

Publications and source records attributed to R Waldherr.

At least 19 recordsLinked to original sources
PubMed2006

Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel pathomechanism for dense deposit disease (MPGN II).

We report a novel pathomechanism for membranoproliferative glomerulonephritis type II (MPGN II) caused by a mutant Factor H protein expressed in the plasma. Genetic analyses of two patients revealed deletion of a single Lys residue (K224) located within the complement regulatory region in domain 4 of Factor H. This deletion resulted in defective complement control: mutant protein purified from the plasma of patients showed severely reduced cofactor and decay-accelerating activity, as well as reduced binding to the central complement component C3b. However, cell-binding activity of the mutant protein was normal and comparable to wild-type Factor H. The patients are daughters of consanguineous parents. As both patients but also their healthy mother were positive for C3 nephritic factor, the mutant Factor H protein is considered relevant for unrestricted activation of the disease-causing activation of the alternative complement pathway. Replacement of functional Factor H by fresh frozen plasma (10-15 ml/kg/14 days) was well tolerated, prevented so far disease progression in both patients, and is in the long run expected to preserve kidney function.

Amino Acid Sequence↗
PubMed2006

Mesangial IgA deposition in minimal change nephrotic syndrome: coincidence of different entities or variant of minimal change disease?

BACKGROUND: Mesangial deposition of IgA (MCA) is a very rare finding in minimal change disease and has previously been considered a pure coincidence. In the U.S. and Europe only anecdotal case reports exist. To date, there has been no consensus on nomenclature and categorization of this entity. We describe 2 cases of MCA with analogue histological findings but relevant differences in clinical presentation, and we discuss the clinical implications of mesangial IgA deposition in minimal change nephrotic syndrome. PATIENTS: A 47-year-old female was admitted to hospital with nephrotic syndrome, microscopic hematuria, arterial hypertension and slight impairment of renal function 3 weeks after an unspecific upper airway infection. A 42-year-old male presented with nephrotic syndrome, microscopic hematuria, normotension and normal renal function. Both of the nephrotic syndromes were steroid-responsive and steroid-dependent. FINDINGS: The clinical presentation of the male patient was consistent with the features of minimal change glomerulopathy, whereas the female patient combined signs of minimal change disease and IgA nephropathy. Light microscopy revealed mesangial IgA immune deposits and slight mesangial hypercellularity. Electron microscopic studies of MCA patients disclose diffuse effacement of glomerular foot processes. CONCLUSION: Our cases and a review of the literature indicate that the histological diagnosis of MCA may comprise different pathogenetic entities. From the clinical point of view, MCA has to be regarded as a minimal change nephrotic syndrome with symptomatic or asymptomatic mesangial IgA deposition. IgA deposition constitutes a risk factor for impairment of renal function and indicates a frequently relapsing course.

Adult↗
PubMed2005

Dihydrotachysterol therapy for hypoparathyroidism: consequences of inadequate monitoring. Five cases and a review.

BACKGROUND: The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions. PATIENTS AND METHODS: Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment. RESULTS: All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level. CONCLUSIONS: In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.

Aged↗
PubMed2005

Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis.

In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T(reg)) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T(reg) cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4(+) lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25(+) cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4(+) CD45RB(high)) population only. FOXP3 mRNA expression in CD4(+) T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P < 0.01). PBMC of AAV patients produced significantly less interleukin (IL)-10 and interferon (IFN)-gamma after anti-CD3/CD28 stimulation. The percentage of IL-10 and IL-12, but not IFN-gamma, IL-4 or tumour necrosis factor (TNF)-alpha-producing cells was significantly higher in patients compared to HC. These findings were confined to the memory population of CD4(+) cells. We conclude that AAV patients are lymphopenic and have low numbers of CD4(+) T cells, which seem to be in a persistent state of activation.

Adult↗
PubMed2005

Nephrolithiasis and hematuria--sometimes a stony road to diagnosis.

We report a case of a young man with a history of kidney stones. Occurrence of gross hematuria several months after the extracorporeal shock wave, lithotripsy (ESWL) treatment lead to hospitalization. By ultrasound and abdominal CT scan, the urologist could exclude post-renal causes of the gross hematuria and acute renal failure. After transfer to a department of nephrology hemodialysis was started, an immediate kidney biopsy was performed and prednisolone was administered on the same day. The kidney biopsy revealed an anti-glomerular basement membrane (GBM) disease. The renal function did not recover and the patient remained on hemodialysis. In the literature it has been hypothesized that ESWL-treated patients are prone to develop anti-GBM disease by liberation of glomerular basement antigen through the ESWL high energy shock waves. An additional hypothesis considering the higher susceptibility for anti-GBM disease among certain HLA-tissue types is discussed with regard to our case. Unfortunately, the prolonged track to diagnosis and delayed immunosuppressive treatment could not prevent poor clinical outcome. Although anti-GBM disease is a rather rare disease, it should be included as a differential diagnosis for hematuria--especially months after ESWL treatment. Otherwise early diagnosis may be missed and as in our patient immunosuppressive treatment will remain unsuccessful to recover renal function.

Adult↗
PubMed2003

Expression of somatostatin receptors in inflammatory lesions and diagnostic value of somatostatin receptor scintigraphy in patients with ANCA-associated small vessel vasculitis.

OBJECTIVE: To assess the usefulness of somatostatin receptor (SSTR) scintigraphy for the evaluation of disease activity in the upper and lower respiratory tract in ANCA-associated vasculitis (AASV). METHODS: Thirty-two consecutive patients with AASV were subjected to SSTR scintigraphy as part of their initial diagnostic evaluation and follow-up. The presence of SSTRs in inflammatory lesions was evaluated with immunohistochemistry in selected cases. RESULTS: In AASV, specificity of SSTR scintigraphy for active vs non-active disease was 96% for pulmonary disease and 100% for ear, nose and throat (ENT) involvement, while sensitivity was 86% and 68%, respectively. Absence of previously present tracer accumulation characterized treatment responders, and treatment resistance was reflected by repeated positive scintigraphy. We could demonstrate the expression of SSTRs in lung and mucosal biopsies obtained from patients with active Wegener's granulomatosis and with microscopic polyangiitis. CONCLUSION: SSTR scintigraphy is useful for the assessment of AASV, indicating disease activity, disease extent and treatment efficacy. SSTRs are expressed in both granulomatous as well as non-granulomatous AASV.

Adult↗
PubMed2003

Acute hepatitis induced by Greater Celandine (Chelidonium majus).

We report on two cases of acute liver injury along with the intake of Greater Celandine (Chelidonium majus), a well-known herbal remedy frequently used for irritable bowel syndrome. All other possible causes of acute liver damage were excluded in both patients. In one patient, cholestatic hepatitis recurred rapidly after involuntary re-exposition. Both patients fully recovered after the withdrawal of Greater Celandine. The two cases add to the existing database about the potential hepatotoxicity of drugs containing Greater Celandine and raise the question whether the approval of this drug should be re-evaluated in the light of lacking evidence for a therapeutic benefit.

Adult↗
PubMed2003

Inhibition of alcohol-associated colonic hyperregeneration by alpha-tocopherol in the rat.

BACKGROUND: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether alpha-tocopherol supplementation may prevent ethanol-induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis. METHODS: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol + alpha-tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) + alpha-tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti-proliferating cell nuclear antigen (PCNA) or anti-BCL2 antibodies. Fractional (k(s)) and absolute (V(s)) rates of protein synthesis and rates of protein synthesis relative to RNA (k(RNA)) and DNA (k(DNA)) were measured with a flooding dose of L-[4-3H] phenylalanine with complementary analysis of protein and nucleic acid composition. RESULTS: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 +/- 2.3 vs. control, 6.51 +/- 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor k(s), k(RNA), k(DNA), and V(s) were affected. This increase in PCNA index was significantly diminished by coadministration of alpha-tocopherol (ethanol + alpha tocopherol, 7.86 +/- 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 +/- 4.4 vs. control, 12.1 +/- 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor alpha tocopherol feeding had any significant effect on BCL-2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption. CONCLUSIONS: Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with alpha-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation.

Animals↗
PubMed2003

Improved clinical outcome of lupus nephritis during the past decade: importance of early diagnosis and treatment.

OBJECTIVE: To evaluate the differences in the outcome of lupus nephritis diagnosed either in the 1980s or the 1990s in Heidelberg, Germany. METHODS: Fifteen patients with biopsy confirmed lupus nephritis (LN) were followed up between 1980 and 1989 and 41 patients were followed up between 1990 and 2000. Their status at diagnosis and their treatment schedules and outcome were analysed. 68% had WHO IV nephritis. RESULTS: In the decade from 1990 to 2000 there was significantly less proteinuria (46 v 17 g/l, p=0.008), significantly lower rates of renal failure (40% v 17%, p=0.02), and fewer histological signs of chronicity (33% v 10%, p=0.01) at the time of diagnosis of LN than in the decade from 1980 to 1989. The mean (SD) time from the first appearance of proteinuria until kidney biopsy was significantly shorter in the later decade (15.4 (15.6) v 3.9 (4.7) months). Although treatment schedules were not significantly different, the outcome of the disease was significantly better in the patients who were diagnosed with LN between 1990 and 2000 (p=0.045). Whereas 6/15 (40%) patients between 1980 and 1989 had terminal renal failure after a mean time of 94 months, in the group of 1990-2000 no patient developed terminal renal failure (median observation time 24 months). In both groups one patient died from infection. A high chronicity index in histology and the presence of arterial hypertension or renal failure, or both, at the time of diagnosis were significant risk factors for the development of terminal renal failure in the course of the disease. CONCLUSIONS: The outcome of patients with newly diagnosed LN was significantly better between 1990 and 2000 than between 1980 and 1989. Kidney damage and chronic histological changes at time of diagnosis were significantly less common between 1990 and 2000, which is attributable to earlier diagnosis and treatment in the later decade.

Adolescent↗
PubMed2001

Increased rectal cell proliferation following alcohol abuse.

BACKGROUND: Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers. METHODS: Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53. RESULTS: Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis. CONCLUSION: Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.

Adult↗
PubMed2001

Effects of all-trans retinoic acid on renin-angiotensin system in rats with experimental nephritis.

We previously demonstrated that all-trans retinoic acid (RA) preserves glomerular structure and function in anti-Thy1.1 nephritis (Wagner J, Dechow C, Morath C, Lehrke I, Amann K, Floege J, and Ritz E. J Am Soc Nephrol 11: 1479-1489, 2000). Because the renin-angiotensin system (RAS) contributes to renal damage, we 1) studied retinoid-specific effects on its components and 2) compared the effects of all-trans-RA with those of the AT(1)-receptor blocker candesartan. Rats were pretreated for 3 days before injection of the OX-7 antibody and continued with treatment with either vehicle or daily injections of 10 mg/kg all-trans-RA only (study 1) or 10 mg/kg body wt all-trans-RA, 1 mg/kg candesartan, or both (study 2) for an additional 7 days. The blood pressure increase observed in anti-Thy1.1 nephritic rats was equally normalized by all-trans-RA and candesartan (P < 0.05). In nephritic rats, mRNAs of angiotensinogen and angiotensin-converting enzyme (ACE) in the kidney were unchanged, but renin mRNA was lower (P < 0.01). Renal and glomerular AT(1)-receptor gene and protein expression levels were higher in anti-Thy1.1 nephritic rats (P < 0.05). In the renal cortex of nephritic rats, pretreatment with all-trans-RA significantly reduced mRNAs of all the examined RAS components, but in the glomeruli it increased ACE gene and protein expression (P < 0.01). In nephritic rats, candesartan reduced the number of glomerular cells and mitoses (P < 0.05) less efficiently than all-trans-RA (P < 0.01). Both substances reduced cellular proliferation (proliferating cell nuclear antigen) significantly (P < 0.05). No additive effects were noted when both compounds were combined. In conclusion, all-trans-RA influences the renal RAS in anti-Thy1.1 nephritis by decreasing ANG II synthesis and receptor expression. The beneficial effect of retinoids may be explained, at least in part, by reduction of RAS activity.

Angiotensin II↗
PubMed2001

Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, cultured in high glucose medium.

AIM: A decrease in glomerular heparan sulfate (HS) proteoglycan (PG), without apparent decrease in HSPG core protein expression, has been reported to occur in diabetic nephropathy (DN). In most studies however, agrin, the major HSPG core protein in the glomerular basement membrane, has not been studied. This prompted us to study the glomerular expression of agrin in parallel to the expression of HS-glycosaminoglycans (GAG) in biopsies of patients with DN. Furthermore, the influence of glucose on agrin production in cultured podocytes and the expression of agrin in fetal kidneys was investigated. METHODS: Cryostat sections of renal biopsies from patients with DN (n = 8) and healthy controls (HC, n = 8), were stained for agrin and HS-GAG. Sections of fetal kidneys were double stained for agrin and CD35 or CD31. Stainings were performed by indirect immunofluorescence (IIF). The production of agrin by cultured human podocytes was tested by ELISA and IIF. RESULTS: The expression of agrin, detected by AS46, was significantly reduced in biopsies from patients with DN compared to HC (p < 0.01). Similar findings were observed when monoclonal antibody JM72 was used (p < 0.05). In addition, a significant reduction in the glomerular expression of HS-GAG was detected with JM403 in these patients (p < 0.01). Agrin is expressed in cultured podocytes, the expression hereof was reduced when the cells were cultured in the presence of 25 mM D-glucose (p < 0.01). In biopsies of human fetal kidneys, glomerular expression of agrin coincided with the expression of CD31. In early stages of glomerular differentiation there was a strong staining for agrin and CD31 while CD35 was only slightly positive. CONCLUSIONS: Our data argue against a selective dysregulation in HSPG sulfation in DN, but suggest a pivotal role for hyperglycemia in the downregulation of agrin core protein production.

Aged↗
PubMed2000

Impact of the Banff '97 classification for histological diagnosis of rejection on clinical outcome and renal function parameters after kidney transplantation.

BACKGROUND: Data on a systematic correlation of specific pathomorphologic lesions in renal allograft biopsy specimens with clinical outcome parameters are crucial to determine the relevance of kidney biopsy findings after transplantation for graft prognosis. Specific histologic lesions of the revised Banff '97 classification were correlated with clinical follow-up data. METHODS: The analysis was done on a series of 48 consecutive renal allograft biopsy specimens. Logistic regression was used to compare for response to rejection treatment dependent on histologic grading. Cox regression was applied to analyze the impact of the histologic findings on graft failure during ongoing follow-up. RESULTS: Severity of acute rejection was statistically associated with unresponsiveness to antirejection treatment (odds ratio 2.39, 95% confidence interval 1.13-5.03) and predicted an increased risk of graft failure (hazard ratio 2.16, 95% confidence interval 1.48-3.14). Intimal arteritis (hazard ratio 1.85, 95% confidence interval 1.40-2.45) was the only determinate of a poor survival prognosis. Mean serum creatinine level and the need for antihypertensive drugs were significantly higher in the Banff I-III graded groups after 1 and 2 years of follow-up, whereas patients with borderline rejection were not significantly different from the control group. CONCLUSION: We confirmed a significant association between the revised Banff '97 classification and graft outcome. Intimal arteritis was the only significant predictor of a poor survival probability. The distinction of borderline rejection and Banff grade I rejection seems to be important from a prognostic point of view.

Acute Disease↗
PubMed2000

A case of Perlman syndrome: fetal gigantism, renal dysplasia, and severe neurological deficits.

We report on a neonate presenting with polyhydramnios; macrosomia; macrocephaly; visceromegaly including bilateral nephromegaly, hepatomegaly, cardiomegaly; thymus hyperplasia; cryptorchidism; generalized muscle hypotonia; and a distinctive facial appearance. The clinical course was marked by severe neurodevelopmental deficits combined with progressive respiratory decompensation leading to death at the age 6 months. Magnetic resonance imaging (MRI) disclosed a generalized cerebral atrophy with a marked deficit of the white matter. Renal ultrasound and MRI showed markedly enlarged kidneys with multiple small cystic lesions, a pattern indistinguishable from polycystic kidney disease. The postmortem kidney biopsy revealed dysplastic changes, microcysts, and a focal nephrogenic rest, characteristic features of the Perlman syndrome. In children with fetal gigantism, renal abnormalities, and neurological deficits, Perlman syndrome should be considered and may be confirmed by kidney biopsy.

Abnormalities, Multiple↗
PubMed2000

Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.

Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.

Adolescent↗
PubMed1999

Clinical outcome of Schönlein-Henoch purpura nephritis in children.

We studied the long-term outcome of 64 children with biopsy-proven Schönlein-Henoch purpura (SHP) nephritis over 1-23 years of follow-up. Overall renal survival 10 years after onset was 73%. Multivariate logistic regression analysis identified initial renal insufficiency (P=0.004), nephrotic syndrome (P=0.037), and the severity of histological alterations, as defined by the proportion of glomerular crescents (P=0.051), as significant independent predictors of progressive renal failure. Four patients followed for more than 19 years showed glomerular damage after transient recovery. Eight children with crescentic nephritis associated with a rapidly progressive course and/or persistent nephrotic syndrome were treated by at least seven sessions of plasma exchange (PE) within 16 weeks of onset of purpura. During treatment serum creatinine levels dropped in each patient from a mean of 2.3 to 1.1 mg/dl, followed by a rebound increase. Repeated courses of PE in 5 patients produced comparable responses. Four patients undergoing PE reached end-stage renal disease at 1.2.-3.7 years after onset, whilst 3 finally were in preterminal renal failure (creatinine 3.2-6.1 mg/dl after 7-13.5 years), and 1 patient reached a normal glomerular filtration rate. Our experience suggests that initial renal insufficiency is the best single predictor of the further clinical course in children with SHP nephritis. Early PE appears to delay the progression in some patients with severe, rapidly progressive forms of the disease.

Adolescent↗
PubMed1999

Edmund Randerath (1899-1961): experimental proof for the glomerular origin of proteinuria.

A century ago, Edmund Randerath (1899-1961), who was one of the pioneers in nephrology that provided indirect experimental proof for the glomerular origin of proteinuria, was born. In the first decades of this century, the concept prevailed that "nephrosis" was a process of primary tubular cell degeneration. In contrast to prevailing opinion, he interpreted these changes to be the result of the uptake and storage of serum proteins after they had been filtered in the glomerulus. Edmund Randerath proved the glomerular origin of proteinuria by astute experiments in amphibia. In the salamander, an intraperitoneal injection of albumin provoked the supposedly "degenerative" changes of tubular epithelial cells in only those nephrons that drained the coelomic cavity and were devoid of glomeruli, but not in those nephrons that were closed and attached to glomeruli. This observation provided incontrovertible evidence that the presence of serum proteins in tubular fluid was a prerequisite for the development of the tubular epithelial cell changes typically seen in nephrotic patients.

Animals↗