In this narrative review, we summarize the current knowledge on RNA-based therapies used in rare and ultrarare disorders and congenital diseases in which the kidneys may be involved. In these therapies, RNA molecules are packaged into delivery vehicles to reach the desired target. We describe only drugs that have been approved or are under review for approval by the US Food and Drug Administration and/or the European Medicines Agency. We describe the potential therapeutic role of microRNA (miRNA) in Alport syndrome, polycystic kidney disease and renal cell carcinoma. Notably, large randomized clinical studies are required before these drugs can be introduced into clinical practice. The therapeutic effects of short interfering RNA molecules have been tested and evaluated in patients with various congenital or acquired diseases, such as primary hyperoxaluria, hereditary transthyretin amyloidosis, acute kidney injury after cardiovascular intervention or kidney transplantation (i.e. delayed graft function), and in individuals affected by hypercholesterolemia. In addition, synthetic antisense oligonucleotides have proven effective in patients with moderate or severe hypercholesterolemia who developed statin side effects, such as myalgia or rhabdomyolysis, and in individuals with amyloidosis. These new therapeutic approaches need to be validated through global clinical trials in which large patient samples can be enrolled. Nonetheless, some of these promising new approaches are currently undergoing evaluation for the treatment of common diseases, such as hypertension and diabetes, which are the main causes of chronic kidney disease.

Chronic inflammation in inborn errors of immunity(IEI) caused by the infections or immune dysregulation is associated with the amyloid A (AA) amyloidosis development. This study aims to analyze the clinical characteristics, management strategies, and outcomes of patients with IEI complicated by AA amyloidosis, focusing on demographics, disease manifestations, treatment modalities, and survival rates. Thirteen patients diagnosed with IEI and AA amyloidosis, along with an additional 10 patients previously reported from Türkiye, were reviewed retrospectively. The median ages at diagnosis of IEI and amyloidosis were 20 years (2-61) and 25 years (7-70), respectively. Renal (74%) and gastrointestinal involvement (44%) were the most common, followed by skin(9%), pulmonary (9%), and cardiac involvement (9%). Primary antibody deficiencies(48%), combined immunodeficiencies(31%), hyperimmunoglobulin E syndrome(9%), congenital neutropenia (4%), autoinflammatory disorders (4%), and chronic mucocutaneous candidiasis (4%) were the IEI types associated with amyloidosis. Bronchiectasis (74%) and malignancy (17%) were observed in given ratio of patients. Treatment modalities for amyloidosis include colchicine (n = 12, 52%), steroids (n = 5, 22%) and tocilizumab (n = 2, 9%) without significant benefit. Thirteen patients (57%) died with a median age of 24 years (8-45), predominantly due to sepsis (52%). Familial Mediterranean fever (FMF) gene analysis was negative in all patients except for one, who had a heterozygous MEFV gene defect (M694V). AA amyloidosis in IEI is associated with severe morbidity and mortality. Early diagnosis and management of IEI are crucial to prevent amyloidosis development. However, colchicine appears ineffective once amyloidosis has occurred, highlighting the need for further research into early diagnostic biomarkers and novel treatment options.

Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disorder, characterized by recurrent fever and serositis. It primarily affects individuals of Mediterranean descent, including Arabs, Armenians, Turks, and Jews. The Mediterranean fever (MEFV) gene, responsible for FMF, was discovered in 1997. Biallelic pathogenic variants lead to excessive activation of the pyrin inflammasome, resulting in inflammation. Clinical manifestations include recurrent fever, abdominal pain, and joint involvement, with attacks typically lasting 12-72 hours. Diagnosis relies on clinical criteria and is supported by genetic testing. Colchicine is the primary treatment to reduce attack frequency and prevent the complications like renal amyloidosis. Despite advancements in understanding FMF, including its genetic basis and treatment options, challenges remain in distinguishing it from other autoinflammatory diseases. Co-existing conditions such as juvenile idiopathic arthritis and inflammatory bowel disease are common among FMF patients. Ongoing research should aim to clarify the development of the disease, enhance diagnostic accuracy, and address its clinical presentation and genetic variability, with a focus on identifying new genetic mutations and epigenetic factors that contribute to its pathogenesis.

The objectives of this study were to investigate the clinical biological and histological renal involvement secondary to familial Mediterranean fever (FMF), the epidemiological data, genetics of our patients and their evolution under treatment. We prospectively studied 58 Algerian patients admitted in our nephrology department from January 2012 to January 2021. The diagnosis of nephropathy was suspected clinically and biologically and confirmed histologically. All our patients were tested for MEFV mutations. Results: 58 patients, 30 males and 28 females, mean age 31.68 ± 12.71; 3 (5.17%) chronic dialysis patients and 55 (94.82%) referred to the nephrology department for renal biopsy with renal symptomatology consisting of nephrotic syndrome in 50 (94. 73%), associated with renal failure 27 (47.36%), mainly primary in 23 (34.5%), secondary to seronegative lupus 13 (22.4%), Crohn's disease 9 (14.5%), sarcoidosis 3 (5.26%), and lymphoma 1 (1.7%); 29 (50%) were from consangineous marriages, the histological study found AA amyloidosis in 52 (89.6%); the genetic study confirmed the diagnosis of FMF in 58 (100%). The evolution of the patients: 20 (34.48%) followed in consultation, 25 (43.10%) in hemodialysis and 13 (22.41%) deceased. Conclusion: Renal involvement was the revealing complication in the diagnosis of FMF which exists in our country, and is still underdiagnosed.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.