Introduction to Clinical Renal Medicine (Physiology)

The main functions of the kidneys include:

𖦹 Excreting water-soluble waste

𖦹 Controlling blood pressure

𖦹 Maintaining electrolyte balance

𖦹 Regulating water balance

𖦹 Ensuring acid-base homeostasis

𖦹 Serving endocrine functions, such as producing renin-angiotensin-aldosterone system components, erythropoietin, and activating vitamin D.

The scope of renal medicine includes:

𖦹 Acute kidney injury (AKI)

𖦹 Chronic kidney disease (CKD)

𖦹 Renal replacement therapies

𖦹 Glomerular diseases

𖦹 Tubulointerstitial diseases

𖦹 Acid/base disturbances

𖦹 Electrolyte disturbances

The median life expectancy on RRT after 90 days, categorized by age group for incident patients starting RRT from 2000-2009 varies based on age:

For patients aged 0-14 years: approximately 22.6 years

For patients aged 15-24 years: approximately 30.3 years

For patients aged 25-34 years: approximately 32.2 years

For patients aged 35-44 years: approximately 29.6 years

For patients aged 45-54 years: approximately 25.7 years

For patients aged 55-64 years: approximately 20.1 years

For patients aged 65-74 years: approximately 15.4 years

For patients aged 75-84 years: approximately 9.0 years

For patients aged 85 years and older: approximately 3.6 years

𖦹 Kidney function is typically measured by the volume of fluid filtered from the glomerular capillaries in a specified period of time.

𖦹 In young males, the typical GFR is approximately 130 ml/min/1.73 m^2

𖦹 While in young females, it is approximately 120 ml/min/1.73 m^2.

𖦹 GFR remains stable until around age 40 and then declines at a rate of approximately 1 ml/min/1.73 m^2 per year.

𖦹 At age 80, the mean GFR is approximately half that of a young adult.

𖦹 Blood tests (such as creatinine levels and formulae)

𖦹 Measurement of urine output

𖦹 Assessment of the elimination of radioisotopes

𖦹 GFR is commonly estimated using markers such as creatinine and urea.

𖦹 Creatinine, derived from muscle cells, is the closest to an ideal endogenous marker.

𖦹 Its steady production results in a steady state in plasma, and small changes in creatinine levels reflect large changes in GFR.

𖦹 Urea, though also used, is considered less reliable as its levels are vulnerable to changes for various reasons.

𖦹 GFR can be estimated using formulas that incorporate factors like serum creatinine levels.

𖦹 One commonly used formula is the CKD-EPI equation, which calculates GFR using the following formula: GFR = 141 × min(Scr/κ, 1)^α × max(Scr/κ, 1)^-1.209 × 0.993^Age × 1.018 [if female] Where:

Scr is serum creatinine (mg/dL)

κ is 0.7 for females and 0.9 for males

α is –0.329 for females and –0.411 for males

min indicates the minimum of Scr/κ or 1

max indicates the maximum of Scr/κ or 1

𖦹 Hypovolemia

𖦹 Hemorrhage

𖦹 Volume depletion

𖦹 Hypotension

𖦹 Cardiogenic shock

𖦹 Septic shock

𖦹 Renal hypoperfusion/vasoconstriction

𖦹 NSAIDs (Non-Steroid Anti-inflammatory Drugs)

𖦹 ACE inhibitors or ARBs

𖦹 Abdominal aortic aneurysm (AAA), renal artery stenosis (RAS), or occlusion

𖦹 Hepatorenal syndrome

𖦹 Prostatic obstruction causes 25% of AKI

𖦹 Single remaining kidneys at high risk

𖦹 Can still produce significant amounts of urine

𖦹 Delay in correction (catheter or nephrostomy) compromises renal function permanently

𖦹 Hyperkalaemia refractory to medical therapy: K+ > 6.5 (mmol/L) with ECG changes.

𖦹 Severe Acidosis: pH < 7.25, HCO3 <15.

𖦹 Fluid overload: despite high-dose furosemide appropriate.

𖦹 Symptomatic uraemia: urea > 35 (mmol/L), leading to conditions such as pericarditis and encephalopathy.

𖦹 Hyperkalemia refers to elevated levels of potassium in the blood.

• Presentation of the patient

• Pathogenesis (often poorly understood)

• Histopathology

• Together these factors help us plan the treatment course and optimise patient outcomes

• Asymptomatic urinary abnormalities

• CKD

• Nephrotic syndrome

• Nephritic syndrome

• Rapidly progressive GN (Glomerulonephritis)

Proteinuria quantified by:

•urine albumin:creatinine ratio

•urine protein:creatinine ratio

𖦹 Proteinuria is the presence of an abnormal amount of protein in the urine.

Nephrotic syndrome

• Albumin <30 g/L

• Proteinuria >3g/24 hours

• +/- oedema

Type 2 diabetes

Patients with the following:

𖦹 Diabetes

𖦹 Hypertension

𖦹 History of acute kidney injury (monitor for 3 years even if function back to baseline)

𖦹 Cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease or cerebral vascular disease)

𖦹 Structural renal tract disease, recurrent renal calculi or prostatic hypertrophy

𖦹 Multisystem disease, e.g., systemic lupus erythematosus

𖦹 Family history of end-stage kidney disease (GFR category G5) or hereditary kidney disease

𖦹 Gout

𖦹 Incidental detection of haematuria or proteinuria

𖦹 On nephrotoxic agents such as, lithium, calcineurin inhibitors, sulphasalazine, long term chronic use of NSAIDS

𖦹 Solitary functioning kidney

𖦹 Obesity

𖦹 Diabetes

𖦹 Hypertension

𖦹 Cardiovascular disease

𖦹 AKI

𖦹 Proteinuria

𖦹 Smoking

𖦹 NSAIDs

𖦹 Ethnicity

𖦹 Untreated urinary outflow tract obstruction

𖦹 Inhibiting SGLT2 reduces glucose reabsorption from the glomerular filtrate in the proximal renal tubule.

𖦹 This reduction in glucose reabsorption leads to urinary excretion of glucose and osmotic diuresis.

𖦹 SGLT2 inhibitors also decrease sodium reabsorption, which increases sodium delivery to the distal tubule.

𖦹 Increased sodium delivery to the distal tubule is thought to enhance tubuloglomerular feedback and reduce intraglomerular pressure.

𖦹 The preservation of kidney function by SGLT2 inhibitors is not solely due to their blood glucose-lowering effect and is not limited to patients with type 2 diabetes.

𖦹 Haematological: Anemia due to decreased production of erythropoietin by the kidneys, leading to reduced red blood cell production.

𖦹 Bone: Renal osteodystrophy, a condition characterized by bone mineral density loss, skeletal deformities, and an increased risk of fractures.

𖦹 Cardiovascular (CVS): Increased risk of cardiovascular diseases such as hypertension, heart failure, and coronary artery disease due to fluid overload, electrolyte imbalances, and uremic toxins.

𖦹 Other: Immunological dysfunction, including impaired immune response and increased susceptibility to infections. Malnutrition due to poor appetite, dietary restrictions, and metabolic abnormalities commonly seen in advanced kidney disease.

Acidemia is a medical condition characterized by an abnormally low blood pH, typically below the normal range of 7.35 to 7.45

𖦹 Treating the underlying cause: Identifying and addressing the condition responsible for acidemia is crucial. For example, treating respiratory disorders causing hypoventilation or metabolic disorders causing excess acid production.

𖦹 Intravenous fluids: Administration of intravenous fluids containing bicarbonate can help correct acidemia by buffering excess acids in the blood.

𖦹 Medications: Depending on the cause, medications such as bronchodilators for respiratory conditions or insulin for diabetic ketoacidosis may be necessary.

𖦹 Dialysis: In cases of severe acidemia due to kidney failure (uremia), dialysis may be required to remove accumulated acids and restore normal blood pH.

𖦹 Monitoring: Close monitoring of blood pH levels and electrolyte balance is essential during treatment to ensure correction of acidemia without causing complications.

𖦹 Kidneys 1 α hydroxylate vit D3: The kidneys play a crucial role in activating vitamin D3 by converting it to its active form, 1,25-dihydroxyvitamin D3.

𖦹 Bone mineral disease occurs: Dysfunction in this process can lead to disturbances in calcium and phosphate metabolism, contributing to bone mineral disease.

↓ Glomerular filtration rate: Decreased filtration leads to impaired clearance of phosphate.

↓ Filtered phosphate load: Reduced phosphate clearance results in increased phosphate retention.

Phosphate retention: Elevated phosphate levels contribute to bone demineralization.

↓ 1,25 (OH)2 Vit D3 synthesis → ↓calcium: Decreased activation of vitamin D leads to reduced intestinal calcium absorption.

Directly increases PTH: Elevated phosphate and decreased calcium levels stimulate parathyroid hormone (PTH) secretion.

PTH release: PTH acts on bone and kidneys to mobilize calcium and increase phosphate excretion.

Long term leads to secondary hyperparathyroidism & bone disease:

Definition: Anemia is characterized by a reduced number of circulating red blood cells.

Prevalence: It is common and debilitating, affecting approximately 80% of patients with advanced renal impairment.

Key Indicator: Hemoglobin (Hb) levels serve as a primary indicator of anemia.

CKD Rates: The prevalence of anemia varies with CKD stage:

68% of patients on renal replacement therapy (RRT) experience anemia.

In CKD Stage 3, approximately 5.2% of patients have anemia.

This figure increases to 44% in CKD Stage 4.

HIF Function: HIF is a transcription factor that regulates gene expression in response to changes in oxygen levels.

Erythropoietin (EPO) Production: In hypoxic conditions (low oxygen levels), HIF promotes the expression of the erythropoietin gene (EPO), leading to increased production of EPO.

Iron Metabolism: HIF also regulates genes involved in iron metabolism, including those responsible for iron absorption, transport, and utilization.

Synergistic Regulation: By coordinating EPO production with iron metabolism, HIF ensures that adequate iron is available for hemoglobin synthesis in response to increased erythropoiesis.

𖦹 Definition: Renal failure necessitating renal replacement therapy.

𖦹 Kidney Functions: Toxin elimination, fluid and electrolyte balance, acid-base equilibrium, hormonal regulation.

𖦹 Key Roles: Vitamin D activation, erythropoietin production, metabolic functions.

𖦹 Anaemia management

𖦹 Blood pressure control

𖦹 Diuresis promotion

𖦹 Bicarbonate supplementation

𖦹 Phosphate control

𖦹 Secondary hyperparathyroidism management

𖦹 End-stage renal failure management

𖦹 Non-dialytic management of end-stage renal disease (ESRD)

𖦹 Focuses on optimizing medical therapies to manage symptoms and slow disease progression

𖦹 Includes strategies such as managing anaemia, controlling blood pressure, addressing fluid balance, and treating metabolic abnormalities

𖦹 It's ideal not to delay initiation until the onset of life-threatening complications.

𖦹 Symptoms can be subjectively interpreted; some patients accommodate to them, and medications can mimic symptoms.

𖦹 Quantitative measurements like the estimation of Glomerular Filtration Rate (GFR) are used.

𖦹 MDRD and Cockcroft-Gault equations may overestimate GFR in CKD stages 4 and 5.

𖦹 Diffusion: Occurs when there is a difference in solute concentration on either side of the membrane.

𖦹 Convection: The movement of solute in association with water, also known as solute drag.

𖦹 Georg Haas (1886 - 1971)

𖦹 The Haas dialyzer, developed in 1923, was first used on humans in 1924 in Giessen.

𖦹 Georg Haas treated an acute patient in Giessen in 1926.

𖦹 Willem Kolff (1911-2009)

𖦹 Kolff's first rotating artificial kidney was used for dialysis.

𖦹 Blood passes down one side of a highly permeable membrane.

𖦹 Water and solutes pass across the membrane, including solutes up to 20,000 daltons, such as drugs and electrolytes.

𖦹 Replacement solution with physiologic concentrations of electrolytes is infused.

𖦹 Peritoneal dialysis is a type of dialysis that uses the peritoneal membrane in the abdomen as a semipermeable membrane for fluid and solute exchange.

𖦹 A cleansing solution (dialysate) is infused into the abdomen through a catheter, and waste products and excess fluids pass from the blood vessels in the peritoneal membrane into the dialysate.

𖦹 After a dwell time, the used dialysate is drained from the abdomen, taking waste products with it.

Live donors

𖦹 Related

𖦹 Unrelated

𖦹 Altruistic

Deceased donors

𖦹 Donation after brain death (DBD)

𖦹 Donation after circulatory death (DCD)

𖦹 Measuring renal function

𖦹 Importance of urinary findings

𖦹 Understanding the tempo of the disease

𖦹 General and specific treatments for conditions

𖦹 Managing the patient journey from the onset of kidney problems to kidney failure and beyond