Selected aspects of genetic disorders in chronic kidney disease.

Chronic kidney disease (CKD) can be caused by many conditions. The most common reasons are diabetic nephropathy, hypertension - associated nephropathy, cardiovascular disease. Although there are different reasons of deterioration of kidney function, many of them have combined molecular mechanisms by modulating metabolic homeostasis, autophagy, apoptosis, oxidative stress, inflammation. The aim of this paper is to present known molecular bases of CKD development in the course of other selected diseases to research why different patients are more prone to the CKD than others with the same condition. Selected aspects of genetic conditions were conducted, such as gene polymorphism of sirtuins, APOL1 gene polymorphism, the role of reactive oxygen species. More research is needed to understand the genetics of CKD and its' affecting the process of diagnostics and treatment.

Chronic catheter-related bacteremia of Pseudomonas stutzeri etiology as the cause of membranous-proliferative glomerulonephritis (MPGN) - a case report.

Secondary membranous - proliferative glomerulonephritis most often develops in the course of viral infections (HCV, HBV), autoimmune diseases, paraproteinemia, and also in the course of chronic bacterial infections. Infections with Pseudomonas stutzeri (P. stutzeri) are extremely rare and usually mildly symptomatic. The natural habitat of this bacterium is soil and water. Nevertheless, in the case of P. stutzeri infection, especially in patients frequently hospitalized or receiving immunosuppressive medications, environmental contamination in healthcare facilities should be taken into account when looking for the source of the infection. A CASE REPORT: A 60-year-old man with a previous history of nicotinism and arterial hypertension with a vascular port in the vena cava superior (VCS) after treatment for bladder cancer (stage G2/G3) several years ago was described. The patient underwent the TURBT procedure, and then received intravesical infusions with BCG for 3 years, followed by complications in the form of severe dysuria and lower abdominal pain. Due to severe nausea and the inability to take analgesics orally, the patient was ordered to insert a vascular port into the VCS in order to continue the analgesic and anti - inflammatory therapy. Several years later, after the onset of massive edema of lower limbs, the patient was subjected to a 24-hour urine collection, in which proteinuria amounted to approx. 13 g/day, followed by a diagnostic kidney biopsy. Histopathological examination described membranoproliferative glomerulonephritis (MPGN). Other renal parameters were also abnormal, i.e. serum creatinine concentration was 1.9 mg/ dl and serum urea concentration was 116 mg/dl. Immunosuppressive treatment was initiated. Patient received methylprednisolone intravenously followed by prednisone orally and cyclosporine orally. During the initial period of immunosuppressive therapy, the serum levels of cyclosporine were insufficient (starting from 26.34 ng/ml), which resulted in increasing its dose, ultimately reaching 175 mg/day. After several months of therapy, the patient was hospitalized again, due to infection of the respiratory tract that had lasted for several weeks and was not amenable to antibiotic therapy. Deterioration of renal parameters and increased inflammatory markers suggested diagnosis of catheter - related sepsis. P. stutzeri was grown from the material collected from the catheter and the patient's blood. Appropriate antibiotic therapy was initiated and after the patient's condition improved, cyclosporine therapy was restarted, which was discontinued after the diagnosis of bacteremia. Rapid remission was achieved, allowing the discontinuation of immunosuppressive drugs. CONCLUSIONS: Chronic, asymptomatic infection with a rare pathogen, like Pseudomonas stutzeri, was probably the cause of the glomerulonephritis. After removal of the port and antibiotic therapy, disease remission was achieved.

Cystinuria poorly responding to treatment - the risk of chronic kidney disease.

Cystinuria is the genetic condition for the increased excretion of cystine in the urine. Patients mainly suffer from afflictions related to the presence and passage of kidney stones. The currently available treatment methods include conservative treatment based on increased fluid intake, appropriate diet, medications and urological procedures. The causal treatment has not yet been invented. A CASE REPORT: A patient case was described whose first symptomatic kidney stones appeared after the second year of life. Urinary cystine excretion was significantly increased - 25,431 µmol/1g creatinine (norm: 167-333 µmol/1g creatinine), which was also shown, but lower, in both parents of the patient. Despite the early initiation of therapy including low sodium diet, abundant hydration, alkalization, captopril and compliance with stringent restrictions, the level of urinary cystine excretion was still not within the normal range. There have been many modifications to the therapy and dose increases of drugs, but without visible results. The patient underwent several urological procedures, including: ESWL (Extracorporeal shock wave lithotripsy), URSL (Ureteroscopic lithotripsy), PCNL (Percutaneous nephrolithotomy) and open surgery to remove cystine deposits that were still produced in the kidneys. In addition, for many years the disease was complicated by recurrent urinary tract infections, underweight and lesions like epithelial metaplasia in the bladder. Renal parameters were repeatedly examined. Elevated results such as: serum creatinine 0.9 mg/dl, cystatin C concentration 1.10 mg/l, albumin-creatinine index 0.197, creatinine clearance 50.7 ml/min /1.73 m2 and eGFR 73 ml/min/1.73 m2 allowed for the diagnosis of chronic kidney disease before the age of 18. After many years of conservative treatment, only the introduction of thiopronine, still little known in Poland, reduced the level of cystine excreted in the urine. The inclusion of the drug reduced the tendency to produce kidney stones, which allowed to inhibit the progression of renal failure. CONCLUSIONS: Despite many years of research and modern drugs, cystinuria is still a disease with which patients are associated for the rest of their lives. The ongoing research, along with attempts to understand the genetic and epigenetic mechanisms responsible for the emergence of mutations in the main genes causing the disease and the course of the disease, gives hope for finding a method of causal treatment for cystinuria.