Changes in Novel AKI Biomarkers after Exercise. A Systematic Review.

More than 100 substances have been identified as biomarkers of acute kidney injury. These markers can help to diagnose acute kidney injury (AKI) in its early phase, when the creatinine level is not increased. The two markers most frequently studied in plasma and serum are cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). The former is a marker of kidney function and the latter is a marker of kidney damage. Some other promising serum markers, such as osteopontin and netrin-1, have also been proposed and studied. The list of promising urinary markers is much longer and includes cystatin C, NGAL, kidney injury molecule-1 (KIM-1), liver-type fatty-acid-binding protein (L-FABP), interleukin 18, insulin-like growth factor binding protein 7 (IGFBP-7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and many others. Although these markers are increased in urine for no longer than a few hours after nephrotoxic agent action, they are not widely used in clinical practice. Only combined IGFBP-7/TIMP-2 measurement was approved in some countries as a marker of AKI. Several studies have shown that the levels of urinary AKI biomarkers are increased after physical exercise. This systematic review focuses on studies concerning changes in new AKI biomarkers in healthy adults after single exercise. Twenty-seven papers were identified and analyzed in this review. The interpretation of results from different studies was difficult because of the variety of study groups, designs and methodology. The most convincing data concern cystatin C. There is evidence that cystatin C is a better indicator of glomerular filtration rate (GFR) in athletes after exercise than creatinine and also at rest in athletes with a lean mass lower or higher than average. Serum and plasma NGAL are increased after prolonged exercise, but the level also depends on inflammation and hypoxia; therefore, it seems that in physical exercise, it is too sensitive for AKI diagnosis. It may, however, help to diagnose subclinical kidney injury, e.g., in rhabdomyolysis. Urinary biomarkers are increased after many types of exercise. Increases in NGAL, KIM-1, cystatin-C, L-FABP and interleukin 18 are common, but the levels of most urinary AKI biomarkers decrease rapidly after exercise. The importance of this short-term increase in AKI biomarkers after exercise is doubtful. It is not clear if it is a sign of mild kidney injury or physiological metabolic adaptation to exercise.

Factors influencing post-exercise proteinuria after marathon and ultramarathon races.

Post-exercise proteinuria is one of the most common findings observed after short and intensive physical activity, but is observed also after long runs with low intensity. The aim of this study was to analyze factors influencing proteinuria after marathon runs. Two groups of male amateur runners were studied. The results of 20 marathon finishers (42.195 m), with a mean age of 49.3 ± 6.85 years; and 17 finishers of a 100-km ultramarathon with a mean age of 40.18±4.57 years were studied. Urine albumin to creatinine ratio (ACR) was calculated before and after both races. The relationship between ACR and run pace, metabolites (lactate, beta hydroxybutyrate), markers of inflammation (CRP, IL-6) and insulin was studied. The significant increase in ACR was observed after both marathon races. ACR increased from 6.41 to 21.96 mg/g after the marathon and from 5.37 to 49.64 mg/g after the ultramarathon (p<0.05). The increase in ACR was higher after the ultramarathon that after the marathon. There was no correlation between run pace and proteinuria. There was no correlation between ACR and glucose, free fatty acids, lactate, beta-hydroxybutyrate and insulin levels. There was significant negative correlation between ACR and interleukin 6 (IL-6) (r =-0.59, p< 0.05) after ultramarathon. Proteinuria is a common finding after physical exercise. After very long exercises it is related to duration but not to intensity. There is no association between metabolic and hormonal changes and ACR after marathon runs. The role on inflammatory cytokines in albuminuria is unclear.

Biochemical Markers of Renal Hypoperfusion, Hemoconcentration, and Proteinuria after Extreme Physical Exercise.

Background and Objectives: Physical exercise increases the blood perfusion of muscles, but decreases the renal blood flow. There are several markers of renal hypoperfusion which are used in the differential diagnosis of acute kidney failure. Albuminuria is observed after almost any exercise. The aim of this study was to assess changes in renal hypoperfusion and albuminuria after a 100-km race. Materials and Methods: A total of 27 males who finished a 100-km run were studied. The mean age of the runners was 38.04 ± 5.64 years. The exclusion criteria were a history of kidney disease, glomerular filtration rate (GFR) <60 ml/min, and proteinuria. Blood and urine were collected before and after the race. The urinary albumin/creatinine ratio (ACR), fractional excretion of urea (FeUrea) and sodium (FeNa), plasma urea/creatinine ratio (sUrea/Cr), urine/plasma creatinine ratio (u/pCr), urinary sodium to potassium ratio (uNa/K), and urinary potassium to urinary potassium plus sodium ratio (uK/(K+Na)) were calculated. Results: After the race, significant changes in albuminuria and markers of renal hypoperfusion (FeNa, FeUrea, sUrea/Cr, u/sCr, urinary Na, uNa/K, uK/(K+Na)) were found. Fifteen runners (55.56%) had severe renal hypoperfusion (FeUrea <35, uNa/K <1, and uK/(Na+K) >0.5) after the race. The mean ACR increased from 6.28 ± 3.84 mg/g to 48.43 ± 51.64 mg/g (p < 0.001). The ACR was higher in the group with severe renal hypoperfusion (59.42 ± 59.86 vs. 34.68 ± 37.04 mg/g), but without statistical significance. Conclusions: More than 50% of the runners had severe renal hypoperfusion after extreme exercise. Changes in renal hemodynamics are probably an important, but not the only, factor of post-exercise proteinuria.

Glomerular Filtration Rate Is Unchanged by Ultramarathon.

Wolyniec, W, Ratkowski, W, Kasprowicz, K, Jastrzebski, Z, Malgorzewicz, S, Witek, K, Grzywacz, T, Zmijewski, P, and Renke, M. Glomerular filtration rate is unchanged by ultramarathon. J Strength Cond Res 32(11): 3207-3215, 2018-Acute kidney injury (AKI) is reported as a common complication of marathon and ultramarathon running. In previous studies, AKI was diagnosed on the basis of the creatinine level in serum and estimated glomerular filtration rate (eGFR). In this study, we calculated eGFR and also measured creatinine clearance after every 25 km of a 100-km run. Twenty healthy, amateur runners (males, mean age 40.75 ± 7.15 years, mean body mass 76.87 ± 8.39 kg) took part in a 100-km run on a track. Blood and urine were collected before the run, after every 25 km, and 12 hours after the run. Seventeen runners completed the study. There was increase in creatinine, urea, and uric acid observed after 100 km (p < 0.05). The mean increase in creatinine was 0.21 mg·dl (24.53%). Five runners fulfilled the AKI network criteria of AKI. The eGFR according to the modification of diet in renal disease, chronic kidney disease epidemiology collaboration, and Cockcroft-Gault formulas was significantly decreased after the run (p ≤ 0.05). Otherwise, creatinine clearance calculated from creatinine level in both serum and urine remained stable. In contrast to the majority of previous studies, we did not observe any decrease in the kidney function during an ultramarathon. In this study, the creatinine clearance, which is the best routine laboratory method to determine GFR was used. There is no evidence that long running is harmful for kidney.

Parasitic Infections Associated with Unfavourable Outcomes in Transplant Recipients.

Introduction. The immunosuppression used after transplantation (Tx) is associated with an increased risk of opportunistic infections. In Europe, parasitic infections after Tx are much less common than viral, bacterial and fungal ones. However, diseases caused by parasites are very common in tropical countries. In the last years the number of travellers with immunosuppression visiting tropical countries has increased. Methods. We performed a literature review to evaluate a risk of parasitic infections after Tx in Europe. Results. There is a real risk of parasitic infection in patients after Tx travelling to tropical countries. Malaria, leishmaniasis, strongyloidiasis and schistosomiasis are the most dangerous and relatively common. Although the incidence of these tropical infections after Tx has not increased, the course of disease could be fatal. There are also some cosmopolitan parasitic infections dangerous for patients after Tx. The greatest threat in Europe is toxoplasmosis, especially in heart and bone marrow recipients. The most severe manifestations of toxoplasmosis are myocarditis, encephalitis and disseminated disease. Diarrhoea is one of the most common symptoms of parasitic infection. In Europe the most prevalent pathogens causing diarrhoea are Giardia duodenalis and Cryptosporidium. Conclusions. Solid organ and bone marrow transplantations, blood transfusions and immunosuppressive treatment are associated with a small but real risk of parasitic infections in European citizens. In patients with severe parasitic infection, i.e., those with lung or brain involvement or a disseminated disease, the progression is very rapid and the prognosis is bad. Establishing a diagnosis before the patient's death is challenging.

[Chronic kidney disease - The relevant information for an occupational physician]. / Przewlekla choroba nerek ­ istotne informacje dla lekarza medycyny pracy.

For a number of years chronic kidney disease (CKD) has been listed in the group of lifestyle diseases, such as obesity, diabetes, cardiovascular disease and hypertension. It is estimated that in Poland more than 4 million people may suffer from various stages of CKD. Chronic kidney disease may also be a consequence of all the other civilization diseases. At the same time it is worth noting that nephrological problems are increasingly being taken into account in modern medical certification. The aim of this work is, among other things, to improve safe access to the labor for patients with kidney diseases. In the legislation existing in our country since 2014 it is stated that chronic renal failure is a potential health contraindication to driving. Also in the annex to the Regulation of the Minister of Health dated 9 December 2015 on health conditions required for seafarers to work on a seagoing ship, it is said that ICD-10 codes (International Classification of Diseases) corresponding to acute and chronic renal failure (N17-N19) should be taken into account when qualifying employees to work at sea. Med Pr 2018;69(1):67-75.

[Selected work-related nephropathies]. / Wybrane choroby nerek zwiazane z praca.

Infections, high temperature and many of the toxic substances can cause kidney damage. Acute kidney injury is a well known complication of some work-related diseases, e.g., lead intoxication. Chronic kidney disease can also be caused by some occupational factors. Three work-related nephropathies, in which causal connection with work has been proved, are discussed in this article. There are different risk factors of nephrolithiasis, lead nephropathy and silica nephropathy, but each of them can cause chronic kidney disease. Prevention of these nephropaties seems to be relatively simple. The principles of protection from the toxic effects of heavy metals and silica dust are very specific. The most important prevention of kidney stones is correct fluid intake. In addition to providing adequate quantities of drinking water, it is also important to educate exposed workers and assure enough rest breaks at work.

Impact of hydration with beverages containing free sugars or xylitol on metabolic and acute kidney injury markers after physical exercise.

The proper fluid and carbohydrates intake is essential before and during physical exercise, and for this reason most athletes drink beverages containing a high amount of free sugars. Sweetened soft drinks are also commonly consumed by those not doing any sport, and this habit seems to be both unhealthy and also the cause of metabolic problems. Recently, several sweeteners have been proposed to replace sugars in popular beverages. To examine the impact of free sugars and the popular sweetener xylitol on metabolic profile and the markers of kidney function and injury after exercise the present study was conducted with semi-professional football players. All participants were healthy, with a mean age of 21.91 years. Their sports skills were on the level of the 4th-5th division of the league. The subjects took part in four football training sessions. During each session they drank a 7% solution of sugar (sucrose, fructose, glucose) or xylitol. The tolerability of these beverages and well-being during exercise was monitored. Before and after each training session, blood and urine were collected. The markers of kidney function and injury, uric acid, electrolytes, complete blood count, CRP, serum albumin, serum glucose and the lipid profile were analyzed. The main finding of this study was that the xylitol beverage is the least tolerated during exercise and 38.89% of participants experienced diarrhea after training and xylitol intake. Xylitol also led to unfavorable metabolic changes and a large increase in uric acid and creatinine levels. A mean increase of 1.8 mg/dl in the uric acid level was observed after xylitol intake. Increases in acute kidney injury markers were observed after all experiments, but changes in urine albumin and cystatin C were highest after xylitol. The other three beverages (containing "free sugars" - glucose, fructose and sucrose) had a similar impact on the variables studied, although the glucose solution seems to have some advantages over other beverages. The conclusion is that sweeteners are not a good alternative to sugars, especially during exercise. Pure water without sweeteners should be drunk by those who need to limit their calorie consumption. Clinical Trial Registration: ClinicalTrials.gov, (NCT04310514).

[Mesoamerican nephropathy - a new challenge for occupational physicians]. / Nefropatia mezoamerykanska ­ nowe wyzwanie dla lekarzy medycyny pracy.

Mesoamerican nephropathy (MeN) is an endemic form of chronic kidney disease (CKD) that is not related to risk factors for CKD, such as diabetes and hypertension. It primarily affects men, rural and agricultural laborers, who work in an extremely hot and dry environment. The greatest increase in the prevalence of CKD, particularly since the late 1990s, has been reported in Central America and Southern Mexico, where the prevalence is almost 9 times higher than in the USA. The highest mortality associated with CKD is reported in El Salvador where a 10-fold increase was recorded in 1984-2005. In histological examination, MeN patients manifest tubulointerstitial lesions and, in some cases, also lesions in the glomeruli. The cause of MeN remains unclear. Repeated episodes of occupational heat stress, and sweating accompanied by water loss, have a significant impact on the disease development. The disease is a significant social and economic problem, and a challenge in the field of diagnostics, therapy and prevention for physicians of many specialties, especially for occupational physicians. Med Pr. 2020;71(3):353-61.

Telemedical Maritime Assistance Service at the University Center of Maritime and Tropical Medicine in Gdynia. The analysis of 6 years of activity.

BACKGROUND: In the 1960s, the International Labour Organization passed a convention under which all countries with national shipping were obliged to create a 24-h telemedicine center for ships. In accordance with the convention, Telemedical Assistance Service centers were to provide permanent access to medical advice given by qualified doctors and to create an international platform for the exchange of information and experience. In Poland, the Telemedical Maritime Assistance Service (TMAS) was established in 2012, and its duties in a 24-h system are carried out by doctors from the University Center of Maritime and Tropical Medicine (UCMTM) in Gdynia. The aim of this work was to determine the reasons for medical officers reporting for help from the TMAS doctor on duty and to create a database of the most common diagnoses and actions undertaken, and in particular evacuation. MATERIAL AND METHODS: In the presented work, the authors analyzed TMAS telephony and e-mail advice provided by doctors of the UCMTM in Gdynia, in the period from October 2012 to the end of 2018. RESULTS: In the 6-year period, UCMTM doctors provided TMAS advice 225 times, recommending evacuation in over 20% of these cases. Infectious diseases were the most common cause of contact in the entire period under analysis - 61 cases were recorded, accounting for as many as 27% of all applications. Injuries were the second most frequent reason for seeking help from TMAS, and 20% of TMAS applications (44 cases) were related to trauma. CONCLUSIONS: The obtained data show that TMAS doctors face various medical problems; therefore, providing proper medical assistance to patients requires a close multidisciplinary cooperation between medical officers, TMAS doctors and emergency services. Med Pr. 2020;71(2):121-5.

Gastrointestinal Pathologies in Patients After Successful Renal Transplantation.

BACKGROUND: Kidney transplantation (KT) is the most desired and cost-effective modality of renal replacement therapy for patients with chronic kidney failure. KT protects the patient from complications that may develop during chronic dialysis. Unfortunately, evidence also suggests that KT patients are more prone to developing cancer than healthy persons. Many complications after renal transplantation can be prevented if they are detected early. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after KT. METHODS: Adult patients after KT who are under the care of the Outpatient Department of Nephrology at the Medical University of Gdansk, Poland, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 58 selected patients (36 men and 22 women), endoscopic examination was performed. Mean age was 57.34 ± 10.1 (range, 35-83) years. RESULTS: Out of 940 patients after KT, resting under supervision of the Outpatient Department, 208 patients completed the questionnaire and 118 gave a stool sample for testing: 40 results were positive. After analyzing the questionnaires and stool results, 100 patients qualified for further investigation. The endoscopic examination had been performed so far in 58 patients and revealed gastritis and/or duodenitis in 49 patients, diverticular colon disease in 26, esophagitis in 8, colon polyps in 16, stomach polyps in 4, inflammatory bowel disease in 12, and cancers in 3. CONCLUSIONS: The preliminary results indicate that patients after KT have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.

The Effect of Vitamin D3 Supplementation on Hepcidin, Iron, and IL-6 Responses after a 100 km Ultra-Marathon.

Deficiencies in iron and vitamin D are frequently observed in athletes. Therefore, we examined whether different baseline vitamin D3 levels have any impact on post-exercise serum hepcidin, IL-6 and iron responses in ultra-marathon runners. In this randomized control trial, the subjects (20 male, amateur runners, mean age 40.75 ± 7.15 years) were divided into two groups: experimental (VD) and control (CON). The VD group received vitamin D3 (10,000 UI/day) and the CON group received a placebo for two weeks before the run. Venous blood samples were collected on three occasions-before the run, after the 100 km ultra-marathon and 12 h after the run-to measure iron metabolism indicators, hepcidin, and IL-6 concentration. After two weeks of supplementation, the intervention group demonstrated a higher level of serum 25(OH)D than the CON group (27.82 ± 5.8 ng/mL vs. 20.41 ± 4.67 ng/mL; p < 0.05). There were no differences between the groups before and after the run in the circulating hepcidin and IL-6 levels. The decrease in iron concentration immediately after the 100-km ultra-marathon was smaller in the VD group than CON (p < 0.05). These data show that various vitamin D3 status can affect the post-exercise metabolism of serum iron.

The usefulness of commercially available serological tests in the diagnosis and monitoring of treatment in patients with alveolar echinococcosis.

AIM OF THE STUDY: To assess the clinical usefulness of serological tests in the diagnosis and monitoring of treatment of patients with alveolar echinococcosis (AE). MATERIAL AND METHODS: The results of serological tests, i.e. Echinococcus multilocularis ELISA (Bordier Affinity Products) and Echinococcus Western Blot IgG (LDBIO Diagnostic), of 66 patients were analysed. Duration of follow-up was two years after diagnosis. In the second phase of the study 11 sera obtained from the patients undergoing surgical treatment, in whom the results of Echinococcus Western Blot IgG assay were still positive, were additionally tested with Anti-Echinococcus EUROLINE-WB (IgG) assay. RESULTS: Statistically significant negativization of the Echinococcus multilocularis ELISA test was observed in the group of patients who underwent radical surgery or liver transplantation. Negativization of Echinococcus Western Blot IgG assay results was observed in some patients, among both those who received conservative treatment and those who underwent surgery, but no statistically significant differences were found between treatment groups. In 54.5% of cases the Anti-Echinococcus EUROLINE-WB (IgG) test result was negative when the results of the Echinococcus Western Blot IgG assay were still positive. CONCLUSIONS: Echinococcus multilocularis ELISA proved to be useful in assessing the activity of AE in a group of patients who underwent radical surgery or liver transplantation. The results of our study suggest that Anti-Echinococcus EUROLINE-WB (IgG) is a more dynamic test, which at the time of disappearance of AE activity becomes negative earlier.

Changes in Water Soluble Uremic Toxins and Urinary Acute Kidney Injury Biomarkers After 10- and 100-km Runs.

Acute kidney injury (AKI) is described as a relatively common complication of exercise. In clinical practice the diagnosis of AKI is based on serum creatinine, the level of which is dependent not only on glomerular filtration rate but also on muscle mass and injury. Therefore, the diagnosis of AKI is overestimated after physical exercise. The aim of this study was to determine changes in uremic toxins: creatinine, urea, uric acid, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), trimethylamine N-oxide (TMAO) and urinary makers of AKI: albumin, neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 and cystatin-C (uCyst-C) after long runs. Sixteen runners, mean age 36.7 ± 8.2 years, (2 women, 14 men) participating in 10- and 100-km races were studied. Blood and urine were taken before and after the races to assess markers of AKI. A statistically significant increase in creatinine, urea, uric acid, SDMA and all studied urinary AKI markers was observed. TMAO and ADMA levels did not change. The changes in studied markers seem to be a physiological reaction, because they were observed almost in every runner. The diagnosis of kidney failure after exercise is challenging. The most valuable novel markers which can help in post-exercise AKI diagnosis are uCyst-C and uNGAL.

Ultrasound images in hepatic alveolar echinococcosis and clinical stage of the disease.

PURPOSE: Hepatic alveolar echinococcosis (AE) is a parasitic disease caused by the larval stage of the tapeworm Echinococcus multilocularis. Ultrasonography is the method of choice in the initial diagnosis of AE. The aim of the study is to present the most frequent sonomorphological patterns of lesions in hepatic AE based on the analysis of ultrasound findings in patients treated for AE at the University Centre of Maritime and Tropical Medicine (UCMMiT; Gdynia, Poland), and to establish whether there is a relationship between the clinical stage of AE and the occurrence of a specific sonomorphological pattern of hepatic lesions. PATIENTS AND METHODS: We analysed the results of ultrasound examinations of 58 patients hospitalized in the UCMMiT with probable or certain diagnosis of AE. Liver lesions were assessed according to the classification developed by researchers from the University Hospital in Ulm (Germany). Statistical analysis was based on the relationship between the occurrence of a specific sonomorphological pattern of hepatic lesions and the clinical stage of AE. RESULTS: The most frequently observed patterns of AE lesions in the liver were the hailstorm and the pseudocystic patterns. There was no correlation between the clinical stage of the disease and the ultrasonographic appearance of lesions. There was no statistically significant relationship between the more frequent occurrences of specific ultrasonographic patterns of lesions in the liver and radical or non-radical surgery. CONCLUSIONS: The ultrasonographic appearance of the lesion in liver AE cannot determine the therapeutic management. Treatment plan should be established based on the PMN classification.

Up-regulation of NPY gene expression in hypothalamus of rats with experimental chronic renal failure.

Anorexia is possibly one of the most important causes of malnutrition in uremic patients. The cause of this abnormality is still unknown. Considering that: (a) NPY is one of the most important stimulants of food intake; (b) eating is a central nervous system regulated process and (c) NPY is expressed in hypothalamus, we hypothesized that the decrease of NPY gene expression in the hypothalamus could be an important factor contributing to anorexia associated with uremic state. In contrast to the prediction, the results presented in this paper indicate that the NPY gene expression in the hypothalamus of chronic renal failure (CRF) rats was significantly higher than in the hypothalamus of control (pair-fed) rats. Moreover, we found that serum NPY concentration in CRF rats was higher than in control (pair-fed) animals. The increase of plasma NPY concentration in CRF rats may be due to the greater synthesis of the neuropeptide in liver, since higher level of NPY mRNA was found in liver of CRF rats. The results obtained revealed that experimental chronic renal failure is associated with the increase of NPY gene expression in hypothalamus and liver of rats.

Nicotinamide metabolites accumulate in the tissues of uremic rats.

OBJECTIVE: N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) are nicotinamide (NA) metabolites described by our group and considered to be uremic toxins. Plasma concentration of Met2PY and Met4PY in end-stage renal disease (ESRD) is several-fold higher in comparison with healthy controls. However, there are no data about the concentrations of these compounds in different tissues. The aim of this study was to establish whether the observed high concentrations of these compounds were also present in different tissues of uremic animals. METHODS: This study was conducted in 10 5/6 nephrectomized male Wistar rats and 10 sham-operated animals. Concentrations of nicotinamide and its end products were measured using high-performance liquid chromatography and mass spectrometry. RESULTS: We observed significant elevations of Met2PY and Met4PY in tissues of uremic rats. The greatest differences between healthy and uremic rats were observed in the liver, lungs, and skeletal muscles. Accumulation in the kidney and heart was not so pronounced, but in the case of Met4PY was statistically significant. CONCLUSIONS: We found that Met2PY and Met4PY accumulate not only in the blood but also in tissues of uremic rats.

[Modern treatment of autosomal dominant polycystic kidney disease]. / Nowoczesne leczenie wielotorbielowatego zwyrodnienia nerek typu doroslych.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end stage renal failure (ESRF). Nevertheless, until now the standard therapy of ADPKD consists merely of nephroprotection and treatment of complications. In the sixth decade of life in about 50% of patients renal replacement therapy is initiated. Surgery procedures such as nephrectomy and renal contraction therapy are performed in some patients. In 21st century numerous studies concerning patophysiology of the disease (role of polycystins, intracellular calcium, cAMP) were published and gave an impulse for searching new drugs that could slower progression of ADPKD. Somatostatin receptor agonists, vasopressin V2 receptor antagonists, rapamycin, and tyrosine kinase inhibitors are among medications that are thought to be effective. Although it is unclear if any of these drugs will be really effective there are strong theoretical backgrounds and promising results of experimental studies on animals. Nephrologists and their patients are waiting for the results of clinical trials that are performed now.