Metabolic nephropathies & stone disorders

Mitochondrial diseases are the most common congenital metabolic disorder in the population. They have an important peculiarity, which is that the functioning of the mitochondria depends on proteins expressed by both nuclear genes (Mendelian inheritance) and mitochondrial genes (maternal inheritance).
The main function of mitochondria is to provide energy to the cells for all their functions.

Mitochondrial diseases are serious and systemic diseases, in general, since all the mitochondria in the body
mitochondria in the body can be affected. The organs and systems with the highest oxygen consumption, such as muscles and brain, are the most commonly affected, and because of the relevance of their dysfunction receive the greatest focus in a patient with mitochondrial disease: weakness, fatigue, convulsions, seizures, weakness... are very serious affectations that can detract from the importance of other less expressive organic affectations. For this reason, and despite the fact that the kidney is also an organ with a high energy expenditure (especially at the level of the tubular cells), renal involvement is little studied and described in the literature.

Our project is designed from a multidisciplinary committee (Internal Medicine, Neurology, Biochemistry Laboratory specializing in Mitochondrial Diseases and Nephrology) of the Hospital 12 de Octubre Hospital. Our main objective,
taking advantage of the fact that the scientific community specializing in the field of mitochondrial diseases is making a great effort to improve the characterization of these diseases with a view to the development of new therapies, we believe that the nephrologist should also participate in this.

Renal involvement in these diseases can sometimes lead to the diagnosis of mitochondrial disease itself (as sometimes happens in MIDD: maternally inherited diabetes and deafness), to avoid unnecessary invasive procedures (renal biopsy) or even to avoid immunosuppressive treatments when an erroneous diagnosis is reached (segmental and focal glomerulosclerosis).

As secondary objectives we will study:

1. Whether the level of heteroplasmy in urine can be diagnostic of renal disease (in mitochondrial DNA mutations) 2<
2. If there is an adequate correlation between the renal function estimated by CKD-Epi or MDRD and the real renal function of these patients (it will be measured directly with iohexol and/or cystatin C) since having muscular problems there may be an underestimation with the creatinine-based formulas.

We will perform renal ultrasound, blood tests (biochemistry, blood count and blood venous gases) and urinalysis (eliminations of ions, urine systematic and sediment and albumin/creatinine and protein/creatinine ratios) to all patients undergoing follow-up at Hospital 12 de Octubre who are diagnosed with a mitochondrial disease (confirmed by genetic study)

Data Sources: HCP centre data

Data Elements:

• Demographic data.
• Genotype/mutation identified as causing the pathology. Level of heteroplasmy in blood or other tissues.
• Previous cardiovascular risk factors: hypertension, diabetes, chronic kidney disease, obesity, dyslipidemia.
• Family history of chronic kidney disease.
• Concomitant potentially nephrotoxic treatment.
• Extrarenal manifestations of mitochondrial disease.
• Previous renal function tests.
• Blood pressure, signs/symptoms of renal disease (nocturia, edema, dyspnea).
• Identification of potential nephrotoxic treatment: nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics or antibiotics.
• Identification of nephroprotective treatment: ACEI, ARA2, endothelin receptor antagonists, mineralocorticoid antagonists, iSGLT2.
• Complete renal function analysis:
• Serum analytical studies: Serum cystatin-C and iohexol, serum creatinine, serum urea, venous blood gasometry (pH, bicarbonate concentration), blood ionogram (sodium, potassium, chlorine), phospho-calcium metabolism study (phosphorus, calcium, magnesium, PTH), uric acid, lactic acid, thyroid profile, autoimmunity and ANCA, blood complement levels, electrophoresis and immunofixation, HIV, HCV, HBV serologies. Glycated hemoglobin.
• Analytical studies in urine:
  • Systematic analysis of urine 1 micturition: pH, urinary density, urinary Ionogram (potassium, calcium, phosphorus), uric acid, calculation of transtubular gradients. Urinary osmolarity. Protein/creatinine quotient, albumin/creatinine ratio.
  • 24-hour urine analysis. Proteinuria 24 hours, albuminuria 24 hours. Urinary ionogram (potassium, calcium, phosphorus), uric acid in urine. Electrophoretic study. B2-microglobulinuria. Lactic acid in urine.
  • Urinary tract ultrasound if >2 years since the last urinary tract imaging test.
  • Assessment of mitochondrial heteroplasmy level in urine in those patients with mtDNA mutation.