The combination of diffuse kidney lesions with different diseases of the other organs of the urinary system (the diagnosis, characteristics of the course and outcomes)

The author characterizes in detail 4340 patients with diffuse renal lesions (chronic glomerulonephritis, renal amyloidosis, lupoid nephritis, diabetic glomerulosclerosis and nephrosclerosis) coupled with different diseases of the urinary organs including urolithiasis, cancerous and tuberculous processes, purulent diseases of the kidneys and prostatic lesions. Stage III chronic renal failure (CRF) was revealed in 2073 (57.1%) out of the 4340 patients. All of them died because of uremia. The mean lifespan of the patients was 1.6 +/- 0.1 yr. since manifestation of the concomitant process. The shortest times of CRF onset, the highest frequency of stage III CRF and the least lifespan were noted in patients with double association, particularly in those suffering from associated chronic glomerulonephritis with renal amyloidosis and urinary bladder cancer in the stage of compression with tumor of the intramural parts of the ureters, namely they were 0.6 +/- 0.1, 100% and 1.0 +/- 0.1 yr., respectively. The author holds that the main reason for such an abrupt CRF onset in patients with concomitant renal lesions of any type lies in simultaneous combined influence on the kidneys of absolutely different diseases bearing in mind their etiology and pathogenesis. Besides, according to the author's data, considerable influences on the times of CRF onset and rates of its progress are produced by both the course and stage (phase) of the development of each of the coexistent diseases. Attention is drawn to the necessity of early participation of urologists in the solution of the problems concerned with the policy of managing nephrological patients with diseases of other organs of the urinary system as well as with permanent dynamic follow-up of all the patients with concomitant processes, especially with double ones.     

Functional furosemide loading test. Practical use in children with kidney diseases

Diuretic and aciduretic reactions were compared in healthy children and children with various renal diseases using furosemide loading test. Diuresis, urinary pH, urinary excretion of titered acids and ammonium, and ammonium coefficient were evaluated in healthy controls, patients with chronic and acute renal insufficiency, convalescents after acute renal insufficiency and acute postinfection glomerulonephritis, patients with chronic pyelonephritis, interstitial nephritis, lipoid nephrosis, hematuric chronic glomerulonephritis, and patients with a solitary kidney. Diuresis, urinary pH, ammonium excretion, and ammonium coefficient are proposed as the main test parameters. Patients with the distal tubular acidosis syndrome formed a special group by the results of urinary pH measurements during the third hour of furosemide action. The test helps evaluate the severity of disease and predict its course.     

The ability of partusisten to improve kidney excretory function in the initial stage of kidney failure in patients with chronic glomerulonephritis]

To assess the effect of partusisten (fenoterol) on excretory function of the kidneys, the drug was administered per os in a dose of 10 mg/day for 7-10 days in 17 chronic glomerulonephritis patients with initial forms (stages I-IIA) of renal failure. A dramatic increase of glomerular filtration, a certain rise of tubular reabsorption, a reduction of blood concentration of nitrous residues were revealed, which was accompanied by electrolyte shifts and hemodynamic changes characteristic of partusisten. It is concluded that partusisten can be used as a drug ameliorating excretory function of the kidneys in chronic glomerulonephritis patients with initial forms of chronic renal failure.     

Epithelial cell clusters of distal convoluted tubules in end-stage chronic glomerulonephritis

Differences in the pathologic changes of the proximal convoluted tubules, the cortical segments of the thick ascending limbs of the loops of Henle, and the distal convoluted tubules in the end-stage kidneys with chronic glomerulonephritis were studied by means of both light and electron microscopy. Kidneys with chronic glomerulonephritis were obtained from 8 non-dialyzed patients at autopsy and 9 dialyzed patients at the time of nephrectomy prior to renal transplantation. Epithelial cell clusters with clear cytoplasm, decreases in the luminal and outer diameters of the tubules, and thin basement membranes were observed in both the non-dialyzed and dialyzed kidneys to varying degrees. The epithelial cell clusters were more extensive and distinct in kidneys from patients with a long history of chronic glomerulonephritis and/or long-term hemodialysis. Electron microscopy of the epithelial cell clusters revealed the absence or narrowing of lumens and luminal surfaces that were smooth except for a few short microvilli. Observation of serial sections showed that these epithelial cell clusters were derived from the distal convoluted tubules belonging to obsolescent glomeruli. This form of tubular change is quite different from the well-known atrophy of the proximal convoluted tubules belonging to obsolescent glomeruli in chronic glomerulonephritis.     

The partial recovery of kidney function in chronic uremia patients during hemodialysis treatment

Out of 432 patients placed on the treatment with hemodialysis (HD) for terminal renal failure (TRF) at the All-Union Nephrologic Center from January 1, 1978 to December 31, 1987, 17 patients manifested partial recovery of renal function, which enabled dialysis treatment to be discontinued for a time. Among the 17 patients with noticeable improvement of renal function, 8 presented with lupoid rapid-progressing glomerulonephritis (RPGN), 2 with RPGN associated with hemorrhagic vasculitis, 1 with idiopathic RPGN, 4 with chronic glomerulonephritis (CGN), 1 with chronic pyelonephritis, and 1 with polycystic kidneys. In 11 patients with RPGN, the rate of renal failure progression, expressed by the regression coefficient, was much higher among those in whom HD treatment was discontinued that in the group of patients without renal function recovery. In the 4 patients with CGN, renal function was recovered after the correction of marked disorders of purine metabolism, whereas in the 1 patient with chronic pyelonephritis and in the 1 with polycystic kidneys after urinary infection elimination. According to the ultrasonography data, out of the 17 patients with partial recovery of renal function, the size of the kidneys turned out normal in 14 patients.     

Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia

Kidney tissue from 97 patients was studied by immunofluorescent techniques using antiserum to purified properdin. All patients with acute poststreptococcal glomerulonephritis showed deposition of properdin and the third component of complement (C3), either as "humps" on the basement membrane, or in the mesangium. In all cases of chronic membranoproliferative glomerulonephritis, properdin and C3 were localized in the glomeruli, most commonly in a lobular pattern on the basement membrane. Activation of C3 by the properdin system may explain the depressed serum levels of C3 and terminal complement components even though levels of earlier components are normal, and the deposition of C3, often without immunoglobulins, in the kidneys of patients with acute glomerulonephritis or chronic membranoproliferative glomerulonephritis.     

Evaluation of the indicators of dynamic renal scintigraphy using the radiopharmaceutical preparation In-113m-DTPA in patients with chronic glomerulonephritis before and after heparin therapy

In 70 patients with a morphologically verified diagnosis of chronic glomerulonephritis, functional computer-aided scintigraphy of the kidneys was performed before and after heparin therapy. Improvement in the scintigraphic parameters following heparin therapy was apparent as the reduction of the time of the radiopharmaceutical passage and the decrease of spastic excretory disturbances. A certain deterioration of the scintigraphic parameters after heparin therapy was found in patients with fibroplastic and focal sclerotic glomerulonephritis associated with renal insufficiency.     

The malignant hypertension syndrome: incontrovertible and questionable truths

A total of 42 patients with malignant arterial hypertension (MAH) were examined. Of these, 32 patients had essential hypertension (26 with normal renal function and 6 with renal failure treated by programmed hemodialysis) and 10 suffered from chronic glomerulonephritis. The patients were examined for central hemodynamics, hormonal background (plasma renin activity) (PRA), plasma aldosterone and cortisol concentration. 14 patients underwent closed puncture biopsy of the kidneys. All the patients manifested high PRA associated activation of gluco- and mineralocorticoid adrenal function along with the hyperkinetic syndrome. MAH was characterized by dramatic discrepancy between the stroke and cardiac indices and specific peripheral resistance. Nephrosclerosis whose extent varied, attaining maximum in patients with associated essential hypertension and renal failure and in autopsy material, in addition to severe lesions of the renal vessels appeared to be the common feature of all morphological alterations. Plasmic impregnation and fibrinoid necrosis of the arterioles were not detectable in all the patients, being of focal character. The same alterations were identified in the patients during exacerbation of glomerulonephritis and in the absence of MAH. The data obtained point to the nonuniformity of MAH. Four clinicomorphological variants of MAH are suggested.     

The fluorescent antibody method in the diagnosis of hepatitis B virus infection in glomerulonephritis patients

In 107 patients with glomerulonephritis (GN) (28 were with acute and 79 with chronic GN) and 54 patients afflicted with other diseases of the kidneys, peripheral blood leukocytes were examined for HBsAg by indirect immunofluorescence. In 60 patients with GN and 32 patients with other diseases, blood sera were examined for HBsAg and anti-HBs by enzyme immunoassay along with examination of blood leukocytes for HBsAg. In blood leukocytes of GN patients, HBsAg was detected in 23.4% of cases, whereas in patients afflicted with other diseases of the kidneys, in 5.6% of cases. In the blood serum, HBsAg was also demonstrated more frequently in GN patients (in 15% of cases) as compared to patients with other diseases of the kidneys (in 3.1% of cases). The rate of anti-HBs demonstration did not significantly differ in patients with GN and in those suffering from other diseases of the kidneys. None of the examined patients both with GN and other diseases of the kidneys showed at a time HBsAg and anti-HBs in the serum or HBsAg in leukocytes and anti-HBs in the blood serum. HBsAg in leukocytes and in the blood serum was identified at a time only in one patient afflicted with chronic GN.     

The course of chronic glomerulonephritis in chronic opisthorchiasis

AIM: To characterize clinical, functional and morphological features of chronic glomerulonephritis (CGN) running with chronic opisthorchiasis (CO) and to justify dehelminthization. MATERIAL AND METHODS: Clinical, functional and morphological examinations of the kidneys, immunological characteristics were studied in 100 patients with primary CGN and CO (group 1), 30 patients with CGN free of CO (group 2) and 40 patients with long-term CO. RESULTS: CGN in CO runs with frequent rise of creatinine, glomerular filtration and canal reabsorption fall. Pathogenetic therapy with addition of pulse cyclophosphamide in a dose 10 mg/kg and conduction of dehelminthization a year later lead to long-term remission and inhibition of nephrosclerosis development. CONCLUSION: Clinicofunctional and morphological characteristics of the kidneys in mixed pathology necessitate addition of immunosuppressor cyclophosphamide in a dose 10 mg/kg and dehelminthization in combined treatment of patients with glomerulonephritis and opisthorchiasis.     

Renal biopsy in patients with unexplained renal impairment and normal kidney size

We report renal biopsy findings in 109 patients with unexplained renal impairment (serum creatinine greater than 0.15 mmol/l) and normal-sized non-obstructed kidneys. The most common histological lesions were interstitial nephritis, rapidly progressive glomerulonephritis and a variety of other types of glomerulonephritis. The groups could not be distinguished by the presence or absence of hypertension, haematuria, proteinuria, or features of systemic disease. However interstitial nephritis was found more frequently in patients presenting with one or none of these features and rapidly progressive glomerulonephritis in patients presenting with three or more. All four patients with none of these features had interstitial lesions. Fifty-two per cent of patients with interstitial nephritis improved and 60 per cent of the patients with rapidly progressive glomerulonephritis who received immunosuppressive treatment improved or remained stable with treatment. The benefits of a biopsy diagnosis were almost wholly confined to these two groups. Complications were recorded in nine patients - prolonged macroscopic haematuria in six and symptomatic perirenal haematomata in three. Six required blood transfusion. One required nephrectomy to control haemorrhage and subsequently died. Percutaneous renal biopsy is not without risk in patients with renal impairment but the benefits of diagnosing interstitial nephritis and rapidly progressive glomerulonephritis outweigh the disadvantages.     

Functional and morphological characteristics of a hematuric form of chronic glomerulonephritis

Clinical evidence has been analyzed for 325 patients with chronic glomerulonephritis confirmed histologically. It was established that chronic glomerulonephritis (CG) associated with hematuria exhibits some specific characteristics: great ability for maximal osmotic concentration and partial ability for ammonium excretion in membranoproliferative CG without sclerotic lesions, maximal occurrence in membranoproliferative form of the disease; fibroplastic transformation of the glomeruli is a rare finding. CG with hematuria is worth mentioning in CG diagnosis.     

EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTIKIDNEY SERUM : V. CHRONIC NEPHRITIS OF INSIDIOUS DEVELOPMENT FOLLOWING APPARENT RECOVERY FROM ACUTE NEPHROTOXIC NEPHRITIS

1. Three different inbred lines of rats were found to vary in their response to antikidney serum: rats of the Whelan strain were most susceptible to nephrotoxin and most prone to develop chronic glomerulonephritis immediately following the acute injury induced by this agent; animals of the Evans strain were almost as vulnerable to the acute effects of nephrotoxin; Wistar rats were the least affected. 2. Both Evans and Wistar rats usually recovered quickly from the acute injury, and between the 2nd and 5th months after injection they excreted normal or only slightly abnormal urines. During this period of absence of clinical signs of disease, histopathological examination of their kidneys revealed only minor scarring in the glomerular tufts. 3. Most of these apparently recovered rats subsequently developed a slowly progressing chronic glomerulonephritis irrespective of whether they were fed a basal or high protein diet. 4. Histopathologically similar renal lesions were present in all three strains of rats with active chronic nephritis regardless of whether the chronic disease followed immediately the acute nephrotoxic injury or was separated from it by an interval of months. These lesions were somewhat more severe, however, in Whelan rats. 5. Some intraglomerular scarring was present in the kidneys of all rats which survived acute nephrotoxic nephritis. It was especially prominent in those animals that remained clinically cured for as long as a year. 6. The permanent clinical recovery of certain animals, which were found to have moderate glomerular fibrosis on postmortem examination, suggests that factors other than this residual scarring contributed to the development of the recurrent nephritis observed in most of the Evans and Wistar rats. These unknown factors may produce varying degrees of renal functional trauma affecting both glomeruli and tubules.     

Mechanisms of tubulo-interstitial tissue lesions of the kidneys in chronic glomerulonephritis

The paper is concerned with a study into the mechanisms of renal interstitial lesions of the secondary character seen in patients afflicted with chronic glomerulonephritis. 120 patients with mesangioproliferative and membranous proliferative glomerulonephritis were examined. The patients were distributed into groups depending on the disease acuity, the degree of glomerular sclerosis and the disease stage. Three major mechanisms of the augmentation of changes in the renal interstice have been revealed: 1) exacerbation of the underlying process; 2) the degree of fibroplastic and sclerotic lesions in the glomerulus; 3) drug sensitization.     

THE EXPERIMENTAL INDUCTION OF GLOMERULONEPHRITIS LIKE THAT IN MAN BY INFECTION WITH GROUP A STREPTOCOCCI

106 rabbits received one or more courses of inoculations, spaced 1–4 months apart, with Group A streptococci, usually of strains isolated from patients with acute glomerulonephritis. 8 days to a few weeks after onset of a given infection with streptococci known to have been nephritogenic for man, marked proteinuria, often with hematuria and occasionally with azotemia, was detected in 22 of the animals. 15 of these were sacrificed a few days to a few weeks thereafter, and 10 showed renal changes like those of acute or recurrent acute glomerulonephritis in man. Such changes occurred in three other rabbits whose urine was not examined that died or were sacrificed 1–3 wk after onset of infection with streptococci of a serotype known to include a strain nephritogenic for man. The remaining seven animals in which marked proteinuria had occurred died or were sacrificed many months later, in some cases after additional infections. Two of these had become azotemic and two convulsed and died after giving birth; in these animals, there were renal changes like those that occur in man in chronic latent glomerulonephritis, toxemia of pregnancy super-imposed on chronic latent glomerulonephritis, or chronic active glomerulonephritis. Anatomical changes in the kidneys in the experimentally induced and in naturally occurring glomerulonephritis, from acute to chronic stages, are compared and illustrated. The pathogenesis of poststreptococcal glomerulonephritis is discussed.     

Kidney biopsy in SLE. I. A clinical-morphologic evaluation

The relationship between renal morphology and clinical disease was analysed in 148 patients with SLE attending a lupus clinic. Patients were not selected for renal disease. Renal tissue was assessed according to the World Health Organization classification of lupus nephritis, the presence of active and chronic lesions was recorded and disease activity was measured according to a standard protocol. All sections of the classification were represented in this group of patients. Active and chronic lesions were more likely to occur among patients with Class III/IV (proliferative glomerulonephritis), than in any other category. Patients with Class III/IV biopsy were more likely to have evidence of clinical renal disease than patients in Class II (mesangial). However, almost half of the Class II patients had some evidence of renal disease, including elevated serum creatinine, as well as important non-glomerular lesions. Without biopsy they might have been thought to have proliferative lesions and been treated more aggressively. Two patients with proliferative glomerulonephritis had no clinical evidence of renal disease. Thus, at the time of biopsy results renal histological examination did not uniformly correlate with clinical renal disease.     

Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non-anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.     

AUTOIMMUNE DISEASE IN NZB/BL MICE : I. PATHOLOGY AND PATHOGENESIS OF A MODEL SYSTEM OF SPONTANEOUS GLOMERULONEPHRITIS

This study, based upon 528 laboratory examinations and 16 complete autopsies of NZB/Bl mice, deals with autoimmune manifestations (as shown by hypergammaglobulinemia, Coombs positive hemolytic anemia, and the occasional presence of lupus- and rheumatoid-like factors) and mainly with the pathology and the pathogenesis of glomerulonephritis in these mice, a model system of membranous glomerulonephritis with spontaneous and insidious onset, progression through chronic stages, and almost certainly induced by immunological, and autoimmune, mechanisms. The earliest and lasting histological change was hyaline thickening of the capillary walls and adjacent intercapillary regions of the glomerular tufts, corresponding in location to polysaccharide-rich capillary basement membrane and mesangial materials. Distributed focally and diffusely in the glomerular tuft and eventually sparing no glomerulus, hyaline, granular, and fibrillar ("spongy fiber") materials produced narrowing of capillary lumens by concentric or eccentric encroachment upon them. In the later stages hyaline lobulation and sclerosis of the glomerular tufts occurred. Thus the lesions corresponded to those seen in human focal and diffuse membranous, chronic lobular, and lastly (intracapillary) sclerosing glomerulonephritis. In all instances of glomerulonephritis the glomerular tufts contained selective localizations of mouse immunoglobulins corresponding in distribution to that of the hyaline and (PAS-positive) polysaccharide-rich materials in the focal and diffuse membranous and lobular lesions and in amounts increasing with the severity of glomerular disease. The mouse immunoglobulins were extracted from frozen sections of glomerulonephritic kidneys and were then capable of recombination with glomerular tufts in sections of autologous or isologous glomerulonephritic kidneys from which in vivo localized immunoglobulins had been extracted. The pattern of recombination with glomerular tufts was similar to that of in invo localized immunoglobulins. The extracted immunoglobulins did not show affinity for mouse red cells (in the indirect Coombs test) nor for autologous or isologous cell nuclei (in the immunofluorescence test). The serum of mice with severe glomerulonephritis contained immunoglobulins with in vitro affinity for extracted autologous or isologous glomerular tufts. Thus circulating as well as localized antibodies were demonstrated. The immunogenic materials (autoantigens) may have been formed in the glomerular tufts or accumulated in them from some other source, such as the circulating plasma; however they corresponded in location to polysaccharide-rich capillary basement membrane and mesangial materials. The spleen was identified at the cellular level as the main site of formation of autoantibodies to red cells, as well as the main site of red cell destruction. Some evidence was brought forth suggesting that these autoantibodies were "heavy" or γM-globulins. More studies are in progress.     

Enhanced fractional sodium reabsorption in the ischaemic kidney revisited with lithium as a probe

Extraction of lithium and 51Cr-EDTA across each of the two kidneys was determined during renal vein catheterization in 14 hypertensive patients with unilateral or bilateral renovascular disease before and after i.v. injection of furosemide. Before the administration of furosemide an increased fractional lithium reabsorption was demonstrated across the affected, or more affected kidney. This difference was abolished by furosemide. Using lithium as a probe for sodium, our data suggest an increased fractional tubular sodium reabsorption in the ischaemic human kidney probably located to the proximal tubules as well as to the loop of Henle. Determination of single-kidney fractional lithium reabsorption holds promise as a new research tool for future evaluation of functional abnormalities during divided renal function studies.     

Glomerulonephritis mediated by antibody to glomerular basement membrane. Immunological, clinical, and histopathological characteristics.

A prospective study was undertaken to establish the incidence of glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and its histopathological characteristics in a clinical group of patients presenting with renal disease. Biopsies from 43 of 409 consecutive patients technically satisfactory for direct immunofluorescent (IF) examination had diffuse and generalized linear localization of host immunoglobulin (Ig); two other badly scarred kidneys tested negative to IF although GBM antibodies were eluted. Confirmatory evidence of GBM antibody-mediated disease in these patients came from whole kidney or biopsy elutions (15 patients), serologic assays for circulating GBM antibodies by indirect IF (9 of 38 patients), radioimmunoassay (26 of 34), and hemagglutination (31 of 32). Although sera were not tested from six patients, circulating antibodies were demonstrated by some test in 36 of 39 of the remainder. Histologically, half of the patients had minor and nonspecific glomerular abnormalities or mild focal proliferative glomerulonephritis. More severely involved kidneys had focal necrotizing (17%), rapidly progressive (7%), and chronic, usually sclerosing, glomerulonephritis (27%). Clinical courses of these patients comparably were quite variable, ranging from indolent microhematuria and/or gross hematuric bouts to progressive renal failure; nephrotic syndrome was observed in 11 patients. GBM antibody-mediated glomerulonephritis may be a relatively mild disease with apparently stable renal function, although 16 patients have experienced functional deterioration, and 11 have progressed to dialysis, renal transplantation, or death.