Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist

Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933–1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.

Encephalopathy in a kidney transplant recipient

A 60-year-old man presented several times to the emergency department due to confusion and behavioral changes. He was a kidney transplant recipient dependent on hemodialysis due, presumably, to chronic nephropathy of the transplanted kidney, and was not under any immunosuppressive therapy. He was admitted to the hospital ward due to elevation of C reactive protein and severe proteinuria, leukocyturia and erythrocyturia. The alterations found in the spot urine examination were suggestive of nephritic syndrome, consistent with chronic nephropathy of the transplanted kidney. The neurologic deterioration, however, remained unexplained. CT of the brain and cerebrospinal fluid examination were unremarkable. Infection, auto-immune disease and malignancy were excluded. Corticoid therapy was started for rejection nephropathy. The patient improved dramatically and ultimately the transplanted kidney was removed. Chronic nephropathy of the transplanted kidney was confirmed histologically and the patient remained clinically asymptomatic, without corticoid therapy.

Prevalence and determinants of chronic kidney disease in urban adults’ populations of northern Cameroon: a cross-sectional study

Background: Chronic kidney disease (CKD) is a major health problem with growing prevalence in sub-Saharan Africa. We present the prevalence and determinants of CKD in Garoua and Figuil cities of the North region of Cameroon. Methods: A cross-sectional survey was conducted from January to June 2018 in the two cities, using a multi-level cluster sampling. All adults with low estimated glomerular filtration rate (eGFR) (< 60 ml/min/1.73 m2) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and/or albuminuria (≥ 30 mg/g) were reviewed three months later. Logistic regression models (accounting for the sampling strategy) were used to investigate the predictors of the outcomes. Results: A total of 433 participants were included, with a mean age (95%CI) of 45.0 (43.4-46.6) years, 212 (48.7%) men, 294 (67.9%) from Garoua and 218 (45.6%) with no formal education. Risk factors for chronic nephropathy were highly prevalent including longstanding use of street medications (52.8%), herbal medicines (50.2%) and non-steroidal anti-inflammatory drugs (50%), alcohol consumption (34.4%), hypertension (33.9%), overweight/obesity (33.6%), hyperuricemia (16.8%), smoking (11.3%) and hyperglycemia (6.5%). The prevalence of CKD was 11.7% overall, 10.7% in Garoua and 13% in Figuil participants. Equivalents figures for CKD G3-5 and albuminuria were 2.8%, 2.0% and 4.5%; and 9.1%, 9.3% and 8.5% respectively. History of diabetes, increase systolic blood pressure, hyperglycemia and hyperuricemia were predictors of CKD. Conclusion: The prevalence of CKD is as high in these northern cities as previously reported in southern cities of Cameroon, driven mostly by known modifiable risk factors of chronic nephropathy.

Renal Dysplasia in a Maltese dog

Background: Renal dysplasia (RD) is a common cause of renal failure in young dogs. It is defined as a disorganization in renal parenchymal development, with abnormal differentiation. In all domestic animal species, RD may be hereditary or acquired. The affected animals show clinical signs of early chronic kidney disease, usually between 3 months to 3 years of age. The alterations include persistent metanephric ducts surrounded by primitive mesenchyme, glomeruli and fetal tubules, and abnormal interstitial fibrous tissue. We aimed to report the case of a 1-year-old canine with renal dysplasia.Case: A 1-year-old male Maltese dog experiencing polyuria, polydipsia, recurrent episodic vomiting, bloody diarrhea, weight loss, apathy, and anorexia was referred to a private clinic in the municipality of Itabuna-Bahia. Physical examination revealed hypochromic mucosa, dehydration estimated at 8%, rectal temperature of 37.5º C, halitosis, and a body score of 3 out of 9. Laboratory abnormalities included hematocrit of 18%, with hypochromic normocytic aregenerative anemia, azotemia (urea - 530 mg/dL, creatinine - 10.5 mg/dL), hyperglobulinemia (4.7 g/dL), low urinary density (1005), proteinuria (300 mg/dL), and urinary pH - 7.0. Ultrasonography revealed bilateral small kidneys with loss of cortico-medullary definition, cystic formations of different sizes on the renal surface, and hyperechoic areas in the parenchyma; these alterations were suggestive of bilateral chronic nephropathy. Considering the clinical, hematological, biochemical, and ultrasonographic presentation associated with the age of the patient, renal dysplasia was suspected. The patient's clinical condition progressed to loss of consciousness and convulsions, followed by death. Necropsy revealed pale, hypotrophic kidneys with firm consistency, irregular capsular surface containing multiple cortical cysts of different sizes, and altered cortico-medullar proportion. . Kidney fragments were sent to the Laboratory of Histopathology of the State University of Santa Cruz. Histopathological analysis revealed a marked alteration of renal architecture with glomeruli and immature tubules (adenomatous aspect), persistent primitive mesenchyme, and remnants of the metanephric ducts, as well as tubular dilatation associated with marked interstitial fibrosis, discrete lymphohistiocytic interstitial nephritis, and multifocal areas of mineralization.Discussion: The clinical changes observed in the present case occurred as a consequence of chronic kidney failure caused by RD and included anorexia, apathy, vomiting, bloody diarrhea, polyuria, polydipsia, and dehydration. These alterations were also found in other reported cases. The macroscopic findings were similar to those described in the literature and are characteristic of chronic kidney disease: small, firm, pale-colored kidneys. Microscopic changes of renal dysplasia include persistent metanephric ducts surrounded by primitive mesenchyme, glomeruli and fetal tubules, and abnormal interstitial fibrous tissue. In the histopathological renal evaluation in the present report, morphological alterations compatible with the described alterations in the literature were observed, thus allowing the diagnosis of renal dysplasia. Renal dysplasia can affect young dogs of different breeds, causing clinical manifestations of chronic kidney disease. In view of this, this disease should be included as a differential diagnosis in patients under 3 years old who present signs of chronic nephropathy.