Renal sonography in bipolar patients on long-term lithium treatment.

PURPOSE: The aim of the study was to analyze sonographic (US) renal findings in lithium-treated bipolar patients and to correlate them with renal function. METHODS: Renal US and renal function tests were performed on 120 patients with bipolar disorder. Ninety patients (30 males, 60 females), aged 36-82 years, had received lithium therapy for an average of 16 years, whereas 30 patients (10 males, 20 females), aged 35-85 years, who had never been exposed to lithium, served as controls. RESULTS: In the lithium-treated group, patients with macrocysts (22%) had poorer renal function with higher creatinine serum concentrations, lower estimated glomerular filtration rates, and lower urine specific gravity, compared with the patients without macrocysts. The US changes characteristic for lithium nephropathy (punctate hyperechoic foci, microcysts < 2 mm, and increased echogenicity) were seen in three patients. These patients had been treated with lithium for more than 20 years and had impaired renal function. Sixteen percent of patients in the control group had macrocysts; however, no correlation between their presence and impaired renal function was found. CONCLUSIONS: The presence of macrocysts in the kidneys of lithium-treated bipolar patients is associated with impaired renal function. The US changes characteristic for lithium nephropathy are rare, and in our study, were only found in patients treated with lithium for 20 years or more. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:354-359, 2016.

Novel markers of kidney injury in bipolar patients on long-term lithium treatment.

OBJECTIVES: We assessed kidney function in long-term lithium-treated bipolar patients compared with age-matched patients not taking lithium, including novel markers of kidney injury such as plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta-2 microglobulin (ß2-MG) METHODS: The study comprised 120 patients with bipolar disorder of which 90 (30 males and 60 females) have been receiving lithium for 5-38 (mean 16) years, and 30 (10 males and 20 females) have never been exposed to lithium. RESULTS: Lithium-treated patients, both men and women, showed significantly higher plasma NGAL and urinary ß2-MG and lower urine specific gravity and estimated glomerular filtration rate (eGFR), compared with patients not taking lithium. In these patients, serum NGAL did not correlate with any clinical feature or other parameter of kidney function. Urinary ß2-MG correlated with serum creatinine and eGFR in the whole group of lithium-treated patients and in addition, in males, with duration of illness, duration of lithium treatment, and urine specific gravity. CONCLUSIONS: Lithium treatment causes an impairment of kidney function reflected also by abnormal levels of novel markers of kidney injury. Of these, urinary ß2-MG, as a marker of tubular function seems to be better predictor than serum NGAL in lithium-treated patients because it shows multiple clinical and biochemical correlations, especially in men.

Screening for the markers of kidney damage in men and women on long-term lithium treatment.

BACKGROUND: Lithium is the most effective therapeutic modality for the prevention of recurrences in bipolar disorder. An important adverse effect of lithium, especially with long-term treatment, is a possibility of a toxic effect on kidney function. Therefore, the aim of the study was to assess kidney function in a group of long-term lithium-treated patients. MATERIAL/METHODS: The study comprised 80 patients with bipolar mood disorder (26 male, 54 female), aged 60 ± 11 years. They had been receiving lithium for 5-38 (16 ± 9) years. Random urine sample was examined for albumin and creatinine excretion, and urinary albumin to creatinine ratio (UACR) was calculated. Specific gravity of the urine sample was recorded. Serum concentration of creatinine was measured and estimated glomerular filtration rate (eGFR) was calculated. Serum concentration of albumin was also measured. RESULTS: Decreased eGFR values <60 ml/min/1.73 m² were found in 23% of patients, significantly more frequently in men that in women (38% vs. 16%, p=0.04). Elevated UACR values (>30 mg/g) were found in 25% of men and 12% of women, respectively. Serum albumin concentration >52 g/l was detected in 19% of patients (17% of men and 20% of women). Specific gravity of the urine, equal to or below 1.005, was recorded in 21% of men and 14% of women. CONCLUSIONS: The results confirm the opinion that screening for the markers of kidney damage should be performed in long-term lithium-treated patients for identification of persons with impaired kidney function. Male sex seems to be the risk factor for the development of kidney damage during long-term lithium treatment.

Pregnancy in diabetic woman with coexisting hypothyroidism, coronary artery disease and with early onset nephrotic syndrome--a case report.

We present a case of pregnancy in 28-years old nulliparous woman with an over 20-years long history of diabetes, hypothyroidism, diabetic nephropathy with nephrotic syndrome, retinopathy and coronary artery disease treated with PCA prior the pregnancy (class H diabetes, according to White classification).

[The effect of long-term lithium treatment on kidney function]. / Wplyw dlugotrwalego podawania litu na czynnosc nerek.

In 1963 it was first demonstrated that long-term lithium administration exerts a "mood-stabilising" effect, preventing recurrences of mania and depression in bipolar affective disorder. Despite the introduction of many other drugs having mood-stabilising effect, lithium still remains the first choice drug for the prophylaxis of affective episodes in mood disorder. Lithium is eliminated nearly exclusively by the kidneys: lithium clearance is proportional to creatinine clearance and is influenced by natriuretic and antinatriuretic factors. Nowadays, nearly 40-year experience with long-term lithium treatment point to a possibility of nephrotoxic effects of this ion. Impaired urinary concentrating ability, which, in a few patients can reach an intensity of diabetes insipidus, can occur after several weeks of lithium administration. Favourable results in the treatment of diabetes insipidus have been obtained with amiloride, the drug which block epithelial sodium channel. However, after 10-20 years of treatment, lithium-induced interstitial nephropathy may be demonstrated in some patients, which, in small proportion of the latter may lead to end-stage renal disease. Lithium-induced hipercalcemia and nephrotic syndrome are rare complications of lithium therapy. In patients on long-term lithium therapy periodic monitoring of kidney function by measuring serum creatinine concentration and glomerular filtration rate is necessary. In case of detecting nephropathy, a discontinuation of lithium sho uld be considered. The patient in whom lithium was discontinued due to nephropathy should remain in nephrological treatment.

Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis.

BACKGROUND: The effects of tumor necrosis factor α (TNF α), a potent proinflammatory cytokine, in the kidneys are mediated by two membrane receptors (TNFR), TNFR1 and TNFR2. The expression of both TNF and TNFRs increases in several kidney diseases and is associated with the shedding of the receptors out of the cell membranes. In an experimental model of glomerulonephritis (GN), elevated concentrations of TNFRs in serum and TNFRs excretion in urine were demonstrated. The aim of this study was evaluation of urinary excretion of TNFR1 and its relationship with the clinical markers of kidney injury in patients with GN. The value of basal urinary TNFR1 excretion as a prognostic indicator of the progression of kidney function impairment was also assessed. MATERIAL AND METHODS: Fifty-five patients with newly diagnosed, biopsy-proven primary GN were included in the study. In all patients, and in 20 healthy subjects, UTNFR1 was measured using an ELISA . In the patients, risk factors of the progression of impairment of kidney function (reduced eCcr, nephrotic syndrome, hypertension and intensity of morphological lesions in the kidneys) were evaluated. The appropriate treatment was then introduced and the patients were in follow-up for 4 years. The progression of kidney function impairment was defined as a reduction of eCcr > 5 mL/min/1.73 m2 /year during follow-up. The association of basal TNFR1 excretion with the progression was evaluated. RESULTS: Urinary excretion of TNFR1 in the patients with GN (4039.2 ± 3801.5 pg/mgCr) was greater than in the healthy subjects (1358.9 ± 927.8 pg/mgCr, P < 0,00002). A significant negative correlation between TNFR1 excretion and eCcr (Sr=0.464, P < 0.01) and a positive correlation between TNFR1 excretion and proteinuria (Sr = 0,463, P < 0.01) were found. In 13 patients, a marked reduction of eCcr was observed during follow-up. Logistic regression analysis revealed that TNFR1 excretion > 3863.3 pg/mgCr predicts progression of renal function impairment along with advanced interstitial fibrosis in the kidney biopsy specimens at presentation. CONCLUSION: Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNFα-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.

Elevated urinary fibronectin excretion predicts poor outcome in patients with primary chronic glomerulonephritis.

BACKGROUND/AIMS: Fibronectin (FN) is one of the major matrix proteins in the kidney. The accumulation of FN fragments in inflamed glomeruli could contribute to the progression of renal injury. In the present study, the urinary FN excretion (UFN) was measured for evaluation of its possible role as a prognostic marker in patients with newly diagnosed chronic glomerulonephritis (GN). METHODS: In 55 patients with newly diagnosed biopsy-proven chronic GN, UFN was measured using an enzyme-immunossay kit. The progression of kidney disease was defined as a reduction of the estimated glomerular filtration rate (eGFR) >or=5 ml/min/year during the 4-year follow-up. RESULTS: The mean UFN in patients with GN (245.0 +/- 229.2 ng/mmol creatinine) was higher than in the 19 healthy subjects (100.7 +/- 87.3 ng/mmol creatinine; p < 0.002). No correlations between the initial UFN and eGFR and proteinuria were found. We did not find any association between UFN and the severity of glomerular sclerosis or the intensity of interstitial fibrosis. The progressive fall of eGFR was recorded in 13 patients (progressors). The mean initial UFN was significantly higher in progressors than in nonprogressors (p < 0.01). In logistic regression analysis, the initial high UFN was identified as independent factor predicting kidney function deterioration. CONCLUSION: These results indicate that UFN measured before treatment could serve as an additional prognostic marker of a poor outcome in patients with newly diagnosed primary GN.

Effect of membrane permeability on survival of hemodialysis patients.

The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis.

Early detection of chronic kidney disease: results of the PolNef study.

BACKGROUND: Continuous increase in the number of patients with end-stage renal disease demands early detection of chronic kidney disease (CKD). The aim of the present study was to diagnose CKD in its earliest stages in a randomly selected population using a diagnostic algorithm developed by the working group. METHODS: An algorithm for the diagnostic procedure was created to identify patients with CKD requiring further nephrological care. Randomly chosen adult inhabitants of a city with a population of 60,000 were invited to participate in this study. Screening procedures included a microalbuminuria dipstick test accompanied by blood pressure measurement and medical questionnaire. In further diagnosis of CKD, estimated glomerular filtration rate (eGFR), albumin concentration in urine, urinalysis and ultrasound examination were used according to the algorithm. Multivariate logistic regression was performed to identify associations between participants' characteristics and albuminuria. RESULTS: Out of 9,700 invited subjects, 2,471 individuals participated in the PolNef study. Albuminuria was detected in 15.6% of the investigated population using the dipstick test and thereafter confirmed in 11.9% by the turbidimetric method. The modeling of multivariate logistic regression indicated the following independent predictors of albuminuria: male sex, diabetes, nocturia and hypertension. For people without diabetes and without hypertension, nocturia independently predicted detection of albuminuria. 481 people received a consultation with a nephrologist, and 96% of them were recognized as having CKD. At least 9% of patients with CKD had eGFR by MDRD <60 ml/min/1.73 m(2). Six persons were referred for further treatment because of newly diagnosed kidney tumor. CONCLUSIONS: CKD in early stages occurs frequently in the studied population. The proposed diagnostic algorithm seems to be a powerful tool to identify subjects at risk of CKD. The role of nocturia as an independent predictor of albuminuria, both in the general population and in people without diabetes or hypertension, should be further examined.

Effects of bicarbonate/lactate dialysis solution on the inflammatory response of spontaneous peritonitis in rats undergoing chronic peritoneal dialysis.

BACKGROUND: We evaluated the incidence of spontaneous peritonitis as well as the local inflammatory response and macroscopic changes in the peritoneum during the use of a bicarbonate/lactate-buffered (P) solution in comparison to conventional (D) solutions in rats on chronic peritoneal dialysis. METHODS: Sixty-three male Wistar rats were implanted with peritoneal catheters. After 7 days, the animals were randomly divided into 2 experimental groups (32 rats in D, 31 rats in P) and infused twice daily over the following 4 weeks. RESULTS: After 14 and 23 days, rats dialyzed with D had a higher peritonitis rate than those dialyzed with P. The median number of days until peritonitis occurred was 22 days for the rats in the D group and 29 days for the rats in the P group. Spontaneously infected rats dialyzed with the D solution had higher scores for adhesion formation. CONCLUSIONS: In this animal model, dialysis with P delayed the time to the 1st infection, reduced the overall peritonitis rate and reduced peritonitis-associated peritoneal adhesion formation during chronic peritoneal dialysis.

Effect of intradialytic intravenous administration of omega-3 fatty acids on nutritional status and inflammatory response in hemodialysis patients: a pilot study.

OBJECTIVE: Because omega-3 polyunsaturated fatty acids (PUFAs) may have anti-inflammatory properties, we tested the hypothesis that intradialytic, intravenous omega-3 PUFA treatment, combined with dietary supplementation, can modify the inflammatory response to dialysis, and influence the nutritional status of hemodialysis (HD) patients. METHODS: Twenty HD patients with serum albumin at <39g/L received 100mL of 10% omega-3 PUFA emulsion during 11 consecutive HD sessions. Body mass index (BMI), serum albumin, transferrin, and lipids were measured before and after treatment. Serum interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) levels were determined before and after the HD session at baseline and after 4 weeks of treatment. RESULTS: No adverse events were evident during the study. There were no significant changes in BMI, serum albumin, transferin, total and low-density lipoprotein cholesterol, and triglycerides. Predialysis hsCRP and IL-6 did not change. There was a significant increase in hsCRP (P=.01) and a tendency of IL-6 concentration to increase during the HD session before treatment (P=.067). In contrast, neither hsCRP (P=.21) nor IL-6 (P=.26) changed during the final HD session. Neither urea reduction ratio nor Kt/V changed significantly during the study, but the normalized protein catabolic ratio increased after treatment (P=.003). CONCLUSIONS: Short-term parenteral administration of omega-3 PUFA is safe and well-tolerated by HD patients. The intervention does not significantly influence markers of inflammation or change the nutritional status of chronic HD patients, but it may attenuate the inflammatory response to HD sessions.

[Nephrological care in Wielkopolska-region of Poland in 2009--realization of the united idea]. / Opieka nefrologiczna w Wielkopolsce w 2009 r.--realizacja spójnej koncepcji.

The establishment of net of the dialysis centers within the distance of 50 km each other, created the basis for realization of united idea for organization of nephrological care in the Wielkopolska-region of Poland. Nephrological care consists of both an integrated methods of the renal replacement therapy: hemodialysis, peritoneal dialysis and kidney transplantation and the screening for chronic kidney disease, its early diagnosis and effective treatment which slow-down the progression of the disease. The nephrological ambulatory, associated with dialysis centers and the nephrological departments with dialysis center and ambulatory play an important role in the integrated nephrological care. As the result of an accessibility of nephrological consultation in the ambulatory located about 25-30 km from the patients home, the nephrological care in Wielkopolska region constantly improves.

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.

[Nephrotic syndrome in the elderly. The most frequent causes of the nephrotic syndrome in the elderly (part I)]. / Zespól nerczycowy u osób starszych. Najczestsze przyczyny zespolu nerczycowego w wieku podeszlym (czesc I).

Nephrotic syndrome (NS) is an essential clinical problem in the elderly. It may be difficult to recognize NS in the elderly because its symptoms are frequently missed with congestive heart failure or venous insufficiency. Glomerular diseases are not most common in elderly population but they play important role in renal pathology in this group of patients. Many structural and functional changes occur in the kidney with an increasing age. These changes may make, at least in part, the interpretation of renal lesions difficult. Glomerular pathology in this group of patients may be secondary to neoplastic diseases, and, therefore before the kidney biopsy screening for malignancies should be performed. The occurrence of particular forms of glomerular diseases differs between the older and young population. The most common forms of primary glomerular diseases in elderly are membranous nephropathy and focal-segmental glomerulosclerosis, whereas diabetic nephropathy and amyloidosis are common causes of secondary nephropathies. Kidney biopsy in the elderly gives valuable information, just as it is in the other age groups. It is a reasonably safe procedure, although associated with an increased risk of bleedings, when compared to younger population.

[Nephrotic syndrome in the elderly. Treatment of the nephrotic syndrome in the elderly (part II)]. / Zespól nerczycowy u osób starszych. Leczenie zespolu nerczycowego u chorych w wieku podeszlym (czesc II).

Nephrotic syndrome (NS) in elderly may increase mortality. The severity of NS determines its management. In the milder forms, with serum albumin concentrations greater than 2.5 mg/dl, significant sodium retention, volume expansion and hypertension patients should be treated with diuretics and hypertensive agents alone. Hypercholesterolemia needs to be treated in patients with NS because this is an important contributor to progressive loss of renal function and increased morbidity and mortality from cardiovascular disease in patients with renal insufficiency Statins decrease proteinuria and have antinflammatory action. Patients with severe NS will likely require immunosuppressive agents to significantly reduce heavy proteinuria. Elderly individuals should receive an appropriate immunosuppressive therapy to induce remission of NS and reduce the risk of progressive loss of renal function. However, since side effects of the used drugs and infectious complications occur more frequently in elderly, careful monitoring of therapy should be carried out.

The history of nephrology in Poland.

Modern nephrology developed in Poland mostly from the internal medicine department chaired in Warsaw by the great internist prof. Witold Orlowski (1874-1966). Three of his pupils Tadeusz Orlowski, Jan Roguski and Jakub Penson independently established the foundations of clinical nephrology and renal replacement therapy in different parts of Poland. T. Orlowski and his team worked in Warsaw, where despite developing clinical nephrology and dialysis also performed the first successful renal transplantation in Poland in 1966. Thereafter in 1975 the Institute of Transplantology in Warsaw was established and for several years was the leading research and education center in nephrology and transplantology. J. Penson established a sound clinical nephrology program in Gdansk, where later physiological and biochemical aspects of the kidney were studied by his successors -- A. Manitius and B. Rutkowski in collaboration with S. Angielski and his biochemical team. They were instrumental in establishing a successful program leading to the development of dialysis in Poland during the last twenty years. J. Roguski in Poznan continued the research on water-electrolyte balance, metabolic and endocrine disturbances in renal patients and immunology of glomerular diseases. The first HD treatment was performed in Poznan in 1958 by the group of J. Roguski and coworkers chaired by K. Baczyk. Subsequently, several strong academic centers were established throughout Poland. F. Kokot in Katowice being himself leader of the Polish nephrology for many years created a very active centre well known for its pioneer publications on water- electrolyte, acid- base and endocrine disorders in different stages of chronic kidney disease. F. Kokot and his successor A. Wiecek are also very active and well recognized on an international scale. In Wroclaw a nephrological center was established by Z. Wiktor and later his coworkers Z. Szewczyk and recently M. Klinger. Other valuable academic nephrological centers were created in Kraków (Z. Hanicki, W. Sulowicz), Lublin (Z. Twardowski, A. Ksiazek), Lódz (Z. Orlowski, W. Chrzanowski), Bydgoszcz (A. Nartowicz, J. Manitius) and later Bialystok (M. Mysliwiec), and others. Simultaneously strong academic units were formed in the military hospitals-Lódz (K. Trznadel, M. Luciak) and Warsaw (Z. Wankowicz). The last center was for many years widely known for their studies concerning PD treatment. Pediatric nephrology developed in parallel with adult centers mainly in Warsaw (T. Wysznska, M. Sieniawska, R. Grenda), Wroclaw (Z. Morawska, D. Zwoliska) and Gdansk (M. Uszycka-Karcz, A Zurowska). Several Polish nephrologists were and still are involved in the activity of European and international nephrological societies.

Development of renal replacement therapy in Poland.

Different methods of renal replacement therapy (RRT) were introduced in Poland quite early: peritoneal dialysis (1953), hemodialysis (1958), renal transplantation (1966). Unfortunately due to the lack of resources in the health care budget, caused by an inefficient economic system, the further development of this therapy was very slow and not compatible with patients needs. The situation changed in the 1980s and 1990s when a National Board of Specialists in Nephrology chaired by A. Manitius and later by B. Rutkowski created a special Program for the Improvement and Development of Dialysis. Long-term efforts and pressure by a united nephrological community led to the establishment of a special fund in the central budget of the Ministry of Health. Final success was related to the political and economical changes in our country and region. Nowadays all three main RRT methods are available to all patients with end-stage renal disease and the actual incidence rate of ESRD is comparable with those of developed European countries. The Polish model of RRT development was also a good example for other Central and Eastern European countries and developing regions.

Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed patients.

Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme, catalyzing S-methylation of thiopurine drugs. TPMT exhibits autosomal codominant polymorphism. Patients carrying a variant genotype have low TPMT activity, and produce elevated levels of 6-thioguanine nucleotides (6-TGN) in their red blood cells (RBC). 6-TGN accumulation may result in azathioprine (AZA)-induced bone marrow myelosuppression in the course of treatment with the drug in a standard dosage regimen in patients following renal transplantation. In the current study, TPMT activity (phenotype) and genotype were determined in dialyzed patients, qualified for renal transplantation. TPMT activity was measured in RBC after dialysis by HPLC method. Patients were genotyped for TPMT *2, *3A and *3C variant alleles using PCR-RFLP and allele-specific PCR methods. TPMT activity ranged between 12.2 and 45.5 nmol 6-mMP/g Hb/h (median value 30.6). A significant correlation between TPMTphenotype and genotype was noted: the heterozygous patients (11.5%) demonstrated significantly lower mean TPMT activity as compared to the wild homozygotes (17 +/- 3.6 vs. 32.4 +/- 4.8 nmol 6-mMP/g Hb/h, p < 0.0003). No overlap in TPMT activity values between the group of heterozygous (range 12.2-20.6) and wild-type homozygous patients (range 22.7-45.5) was noted. TPMT activity, established after hemodialysis and TPMT genotyping results seem to be convergent in dialyzed patients, so both methods can be used for the identification of patients with lower TPMT activity. Such tests could be helpful in AZA dose individualization, and thus in reducing the risk of myelosuppression during AZA therapy following renal transplantation.

[Inherited reduced number of nephrons versus primary arterial hypertension]. / Wrodzona zmniejszona liczba nefronów a pierwotne nadcisnienie tetnicze.

The reduced number of nephrons, which was determined during fetal development may play a role as an important factor influencing blood pressure level in adult life. The results of a study which confirmed the involvement of the reduced nephron number in the etiopathogenesis of primary arterial hypertension were published recently. It was demonstrated, that the number of nephrons in the kidneys of hypertensive persons (without kidney disease) was significantly lower than in matched normotensive persons. The mean glomerular volume in hypertensive persons was markedly greater than in normotensives. The inherited reduced nephron numbers may depend not only on environmental influences acting during fetal development (like malnutrition) but also on the genetic factors. The hypothesis was presented that adaptative hypertrophy of less numerous nephrons is associated with the trait of sodium sensitivity of blood pressure. The results of the described studies may be of significant importance for clarification of the pathogenesis of primary arterial hypertension.

The effect of clodronate on bone mineral density and serum osteocalcin in postmenopausal women with osteopenia - a prospective, randomized, placebo-controlled study.

Background. The efficacy of bisphosphonates in treatment of established osteoporosis has been well-documented; less data have been published on their efficacy in the prophylaxis of postmenopausal bone loss in women with osteopenia. The aim of study was to evaluate the effect of clodronate on bone loss in early postmenopausal women with vertebral osteopenia. Materials and methods. Forty five women aged 52.3+/-3.8 yr with a lumbar spine (Spine) t-score between -1 and -2.5 SD received clodronate 400 mg/day or placebo for 12 months. Bone mineral density (BMD) was measured by DXA in Spine and femoral neck (Femur). Serum osteocalcin (OC) was assessed by RIA. BMD and OC were measured at the baseline, after 1 year of treatment and after further 1 and 2 years of follow-up. Results. BMD slightly decreased in clodronate group: Spine by 0.2% after 1 year (N.S.), 0.5% after 2 years (N.S.) and 0.9% after 3 years (P<0.05 vs. placebo group); Femur by 0.2%, 0.9% and 1.3% (N.S.). OC did not change in placebo group but significantly decreased in clodronate group (15.2%; P<0.05). Conclusions. Clodronate 400 mg daily given postmenopausal women with osteopenia is effective in decreasing OC but an effect on BMD is just detectable and its clinical significance is unclear.