Immunosuppressive therapy with cyclophosphamide and prednisolone in severe idiopathic membranous nephropathy.

In idiopathic membranous nephropathy (IMN) immunosuppressive therapy should be reserved for patients with potential risk factors at baseline or who show a progressive course. Cyclophosphamide pulse therapy (CPT) in IMN is not yet widely tested. We carried out a trial of CPT combined with conventional treatment in a group of patients with IMN at a greater risk. The study group consisted of 36 nephrotic adult IMN patients (M, 26; F, 10) with various combinations of risk factors. Mean proteinuria was 11.3 g/day, 47% patients were hypertensive, 78% had tubular changes, and 36% had focal glomerulosclerosis. They were treated with CPT and/or conventional low-dose cyclophosphamide and prednisolone. Median duration of immunosuppression was 14 months and median total cumulative dose of cyclophosphamide 172 mg/kg body weight. At 6 months (6m) remission was achieved in 44% cases and at the 36th month in 73%. None of the patients developed moderate or severe renal failure. Side-effects were minimal. Multivariate analysis of baseline data and the changing course of the disease during therapy showed that tubular changes (P = 0.0025), creatinine clearance at baseline (P = 0.04) and at 6m (P = 0.02), and proteinuria at 6m (P < 0.0001) significantly influenced the therapeutic effect. We conclude that cyclophosphamide (including pulse) and prednisolone can bring significant remission and maintain renal function in IMN with potential risk factors.

[Changes of laboratory hematologic indices in patients with chronic glomerulopathies following treatment with superhigh doses of cyclophosphamide]. / Promeni v niakoi khematologichni laboratorni pokazetali pri bolni s khronichni glomerulopatii sled lechenie sus svrukhvisoki dozi tsiklofosfamid.

41 patients with active glomerulopathies treated with super high doses of Cyclophosphamide were studied. The following indices were followed up dynamically: hemoglobin concentration, number and morphology of erythrocytes, number and morphology of leucocytes and differential count. Hemoglobin concentration and erythrocyte count remain in the reference ranges in most of the patients. They fall more considerably compared to the initial values between the 90-120 day after the treatment. This fall improves spontaneously and does not require discontinuance of the treatment. The single application of super high dose of Cyclophosphamide does not influence significantly the leucopoiesis. Because of the parallel application of glucocorticosteroids no fall of the leucocyte count is observed and they remain in their reference ranges.

[Clinico-therapeutic and microbiological research on the preparation Monaspor in patients with active pyelonephritis]. / Kliniko-terapevtichni i mikrobiologichni prouchvaniia na preparata monaspor pri bolni s aktiven pielonefrit.

The urinary antiseptic efficacy of cefsulodin (Monaspor--Ciba) was studied in 22 patients with active pyelonephritis. The results were considered very good in 81.8% of the patients with urologic infections caused by P. aeruginosa, P. mirabilis and E. Coli. The drug was well tolerated. The microbiological studies in vitro of the urinary antiseptic efficacy of Monaspor on 575 bacterial strains isolated from patients with active pyelonephritis showed that the antibiotic was most active against Pseudomonas sp., beta-streptococcus, Staph. aureus, P. mirabilis.

[Clinical, laboratory and morphological characteristics of mesangioproliferative glomerulonephritis]. / Klinichni, laboratorni i morfologichni osobenosti na mezangioproliferativnite glomerulonefriti.

The mesangioproliferative glomerulonephritis (MPGN) is the most frequent morphological type of primary glomerulonephritis and it was found in 42.7% of the patients studied. The MPGN is not a single nosologic entity which is proved by the immunofluorescent findings, clinical and laboratory characteristics. Several immunofluorescent types with characteristic clinico-laboratory constellation and different etiopathogenesis could be defined. The most clearly defined types of MPGN are those with leading IgA and IgM precipitates. The similar immunofluorescent findings, clinico-laboratory characteristics, course and susceptibility to symptomatic and pathogenetic treatment in MPGN with leading IgG and C3 precipitates lead to the suggestion that there may exist different "phase" states in the course of the different types of MPGN. In spite of some characteristic differences in the symptomatology and course of the different types of MPGN their differentiation is possible only by kidney biopsy.

[Treatment with superhigh corticosteroid doses (pulse therapy) of patients with the idiopathic nephrotic syndrome]. / Lechenie sus svrukhvisoki dozi kortikosteroidi ("pulsova terapiia") pri bolni s idiopatichen nefrozen sindrom.

The results from the pulse therapy of 11 patients with severe nephrotic manifestations of idiopathic nephrotic syndrome are summarized, that had failed to respond to the preceding conventional corticosteroid treatment. Rapid improvement was attained in nine of the patients studied. Best were the results in the patients with "minimum" morphological alterations and with diffuse mesangial proliferation. Favourable effect was obtained also in the patients with glomerular sclerosis and hyalinosis. The failure of treatment in one of the female patients with mesangial proliferation is associated with the adverse unfavourable factors, and in one of the male-patients with glomerular sclerosis and hyalinosis--with severe morphological changes and exhausted functional potentialities of kidneys. The authors admit that the fast favourable effect by the therapeutic schedule used, make it a means of choice in forms of idiopathic nephrotic syndrome with a grave course and failing to respond to the routine treatment.

Fibrin deposits in the glomeruli and fibrin/fibrinogen degradation products (FDP) in the blood and urine in some renal diseases.

In 115 patients with various glomerular diseases and in 23 with chronic pyelonephritis the comparative incidence of glomerular fibrin deposits, and blood and urinary FDP was studied for evaluation of their clinical value. The results of the study indicate that the determination of urinary FDP is the most reliable clinico-laboratory test for the presence of increased intrarenal haemocoagulation. Moreover, the quantitative assessment of urinary FDP could be also used as an index for estimating the activity of the pathological process, the selectivity of proteinuria, the need for anticoagulant therapy, and the prognosis of the disease.

The differential approach in the treatment of chronic glomerulonephritis.

The comparative effects of corticosteroids, immunosuppressive agents, antiinflammatory drugs and anticoagulants have been studied in the different pathomorphologic types of chronic glomerulonephritis in a total of 185 patients with successful renal biopsy. On the basis of the results a guiding scheme is being proposed for the differential approach in the pathogenetic treatment of different pathomorphologic types of chronic glomerulonephritis with a view to obtaining the best results.

[Incidence and characteristics of the hypertension syndrome in chronic glomerulonephritis]. / Chestota i osobenosti na khipertonichniia sindrom pri khronichnite glomerulonefriti.

The authors share their results from the studies on the incidence and characteristic of hypertonic syndrome in 132 patients with chronic glomerulonephritis (ChGN). In that random group, 65.1 per cent had renoparenchymal hypertension (RPH), 34.8 per cent of the patients had RPH among the patients with normal renal function, and with various degrees of chronic renal insufficiency (ChRI) - 95.4 per cent. In 69 patients, the diagnosis was confirmed by puncture biopsy, with a predomination of membranous, membranous-proliferative, IgA and endoproliferative ChGN. With the exception of IgA nephritis, RPH in the rest is found relatively often even in the absence of ChRI. The symptomatics of RPH was relatively poor--most frequently the patients complained of headache--in 48 per cent but patients with ChGN without RPH also had the same complaints--26 per cent. Complaints as dizziness, tinnitus and insomnia were rare. The hypertension was with a short duration (according to anamnestic data)--in 2/3 less than three years and 40 per cent of the patients had hypertonic crises or/and acute left cardiac insufficiency in spite of the relatively little alterations in ECG and fundus of the eye. Those were mainly patients with advanced ChRI. The authors lay stress upon the necessity of complex treatment of renal insufficiency and of hypertension with a view to the improvement of the prognosis of those patients.

[Naniprus treatment of hypertensive crises in patients with kidney diseases]. / Lechenie na khipertonichni krizi pri bubrechno bolni s Naniprus.

After a brief literature survey, the authors share their experience of the treatment of hypertonic crises and acute left cardiac insufficiency of renal patients via Naniprus, a preparation produced in P.R. of Bulgaria. The patients' age was from 11 to 64. With an average basal arterial pressure (AP) 25.2/14.5 kPa during the crises the patients had an average AP of 33.3/20.0 kPa and only three minutes after the initiation of its drop infusion it was reduced to an average of 25. 1/14.7 kPa (p less than 0.001). In one child with severe pulmonary edema in the progress of a hypertonic crisis, in a crisis for rejection of transplanted kidney, they infused Naniprus continuously for 5 days and nights, and in another transplanted patient--7 days and nights, not observing any undesirable effects. The authors recommend Naniprus infusion to be carried out very cautiously, with AP being checked every minute at the beginning at the other side until obtaining the desired and stable result. Each careless or uncontrolled administration of the preparation threatens with severe collapse. In patients with AV-fistulas reddening of the face and eyes as well as headache were observed.

[Proteinuria in the nephropathy of pregnancy and posttoxicosis renal lesion]. / Vurkhu proteinuriia pri nefropatiiata na bremennostta i sledtoksikoznoto bubrechno uvrezhdane.

Proteinuria was studied in 110 females - 28 pregnant with nephropathy of pregnancy with primary late toxicosis and 82 with past history of the disease with a residual proteinuria after childbirth. Selective type proteinuria was more often found both in pregnant women and in those with a past history of nephropathy. The relative share of the pregnant with non-selective proteinuria is considerably greater. After childbirth, in parallel with the decrease of proteinuria quantity, the non-selective one turns to selective in the majority of the cases. The quantity of the excreted proteins, in the urine, of patients with confirmed glomerular lesions, shows no tendency to decrease. The absence of dynamics in proteinuria quantity and its non-selectivity provides grounds to suspect a deeper lesion of the renal filter, retaining the involution of the morbid process and a tendency to its chronification.

Biochemical methods for the assessment of the selectivity of proteinuria.

The authors have elaborated a biochemical technique for the assessment of the selectivity of proteinuria by means of the clearances of ceruloplasmin, haptoglobin and albumin. The results obtained in 69 patients were compared to those established by the method of Cameron and Blanford, as well as by the clearance of alpha2-macroglobulin. No significant differences were found in the indices of proteinuria, as determined by the proposed biochemical technique and by the method of Cameron and Blanford. Thus the diagnostic value of both methods to assess the selectivity of proteinuria could be considered as equal. The additional measurement of the selectivity of proteinuria by means of proteins with considerably high molecular weight (haptoglobin, alpha2-macroglobulin) gave the possibility of recording cases with severely impaired glomerular permeability. In this respect, the use of the clearance of haptoglobulin, particularly the phenotype Hp 2--2, provided valuable diagnostic information in cases in which the routine methods gave borderline values for the index of proteinuria.

[Clinical, biochemical and morphological characteristics of asymptomatic and oligosymptomatic types of chronic glomerulonephritis]. / Klinische, biochemische und morphologische Besonderheiten der asymptomatischen und oligosymptomatischen Formen der chronischen Glomerulonephritis.

The results of our study confirm that an early and certain diagnosis of the asymptomatic and oligosymptomatic forms of the chronic glomerulonephritis is possible only using comprehensive clinical and biochemical investigation methods and partly the renal biopsy. Only with regard to the clinical manifestation the disease has an asymptomatic or oligosymptomatic course. Some laboratory findings have been changed from the beginning of the disease. The degree of these changes as well as the further existence of the asymptomatic or oligosymptomatic form depend on the pathomorphological type of the disease. But even in the cases with a favourable development a gradual reduction of the renal function was observed. The pathologically decreased values of haploglobin and sialic acid reveal the clear activity of the pathological process. These facts emphasize the necessity to perform systematically prophylactic and therapeutic measures in all cases with asymptomatic or oligosymptomatic chronic glomerulonephritis.

[Serum glycoproteins as an index of protein metabolism in advanced chronic kidney failure]. / Serumglykoproteine als Index des Eiweissstoffwechsels bei fortgeschrittener chronischer Niereninsuffizienz.

The results of our investigation show that in patients under conditions of haemodialysis as well as under conservative therapy the changes of the serum levels of haptoglobin and transferrin are more clearly and less difficult to be recognized than those of the total protein and albumin level. Therefore the serum glycoproteins with a short half-life period may successfully be used as index of the protein metabolism in patients with chronic renal insufficiency as well as additional factor for the assessment of the therapeutic success.