Lecture 19: Kidney Labs and Cysts

Agenesis of the Kidney

Bilateral renal agenesis:

Incompatible with life and often associated with other congenital disorders

Potter’s Sequence

Unilateral agenesis:

Solitary kidney enlarges as a result of compensatory hypertrophy

Some patients develop progressive glomerular sclerosis and chronic kidney disease

Ectopic kidney

One or both kidneys fail to migrate and remain in the pelvis

Generally asymptomatic

Rarely a kidney will cross to other side (crossed ectopia)

Horseshoe Kidney

Kidneys fuse early in development

Migration arrested at inferior mesenteric artery

Abnormal anatomy can obstruct outflow

Azotemia

Elevation in blood levels of nitrogen containing compounds

Creatinine - Secreted by skeletal muscle

Blood Urea Nitrogen (BUN)- Product of protein catabolism and breakdown

Uremia

Azotemia + clinical signs and symptoms

progressive weakness, fatigue, nausea, vomiting, pruritis, tremors, altered mental status, eventually: stupor, coma, death

Dehydration, Edema, Hyperkalemia, Metabolic acidosis

Hyperphosphatemia, Hypocalcemia, Secondary hyperparathyroidism, Renal osteodystrophy

Anemia (low erythropoietin), Bleeding diathesis (platelet dysfunction)

Hypertension, Congestive heart failure, Cardiomyopathy, Pulmonary edema, Uremic pericarditis

Nausea and vomiting, Bleeding, Esophagitis, gastritis, colitis

Myopathy, Peripheral neuropathy, Encephalopathy

Sallow color, Pruritus, Dermatitis

Secondary Hyperparathyroidism

High serum Phosphate + Low serum Calcium + High PTH

Kidney Injury

Decline in GFR

Dysregulation of fluid and electrolyte balance

Retention of metabolic waste products

Can result from glomerular, tubular, interstitial, vascular insult

Acute kidney injury (AKI)

Rapid decline in GFR (hours to days)

Generally reversible

Subacute kidney injury

Diminished GFR for 2 days to 3 months

Chronic kidney disease (CKD)

Diminished GFR that is persistently less than 60 mL/min for ≥3 months

End result of all chronic renal parenchymal diseases

End-stage renal disease (ESRD)

Terminal stage of CKD

GFR <5% of normal

Requires hemodialysis or transplant

Azotemia Causes

Prerenal disease: Decrease in renal perfusion caused by atherosclerosis, hypovolemia, NSAIDs (afferent arteriole vasoconstriction)

Intrinsic renal disease:

Glomerular disease

Renal vascular disease

Tubular and interstitial disease

Postrenal: Obstructive nephropathy

Prerenal Disease Causes

Cardiorenal Disease:

Systolic heart failure → decreased renal perfusion → reduced GFR

Hypotension, fatigue, dyspnea, peripheral edema

“Cardiorenal Disease” can also describe cardiac failure caused by increased Renin in renal disease

Hepatorenal syndrome:

Decompensated liver disease → portal hypertension + hypoalbuminemia

Fluid shift into ascites and portal circulation → decreased renal perfusion

end stage liver disease

Poor prognosis

Glomerular Filitration Rate

Good metric of kidneys functional status

Volume of fluid filtered by glomerulus per unit time

Creatinine or Cystatin C

BUN:Creatinine ratio in kidney injury

>20:1 pre-renal cause of renal injury

In dehydration, BUN is reabsorbed to retain fluid and maintain vascular pressure

12:1 to 20:1 intrarenal cause of renal failure

Urine Osmolality in AKI

Prerenal: >500 mOsm/kg - hypoperfused kidneys are trying to retain fluid

Intrarenal: <500 mOsm/kg - Renal tubules are unable to concentrate urine

Postrenal: Depends on tubule function

Fractional Excretion of Sodium (FENa)

Percentage of filtered sodium that is excreted in the urine

FENa < 1% - Prerenal disease

FENa > 1% - Renal disease (Acute tubular necrosis)

Post renal azotemia

Early disease: resembles prerenal azotemia

Later disease: tubular cells are damaged and it resembles intrinsic azotemia

Simple Cysts

Simple Cysts

Single/multiple all sizes up to 10cm

Common with increasing age (>50)

Frequent incidental finding on imaging

Suspect ADPKD if 3 or more cysts or young individuals (<40)

Occasionally symptomatic - Hemorrhage, rapid distension and pain

Usually of no significance

Autosomal Dominant (Adult) Polycystic Kidney Disease

Autosomal Dominant (Adult) Polycystic Kidney Disease

AD inheritance of pathogenic PKD1 or PKD2 LOF

Slower progression of CKD than other forms of ESRD

Spheroid cysts of variable size compressing intervening function nephrons

Generally asymptomatic until renal function declines in 30s-40s

May present with pain or hematuria

Association with liver cysts, berry aneurisms, mitral valve prolapse

Autosomal Recessive Polycystic Kidney Disease

Autosomal Recessive Polycystic Kidney Disease

Autosomal recessive inheritance of LOF PKHD1

Cysts are slender and at right angle with cortex

Oligohydramnios resulting from decreased urine output → pulmonary insufficiency

If a patient survives respiratory distress in the neonatal period, renal function may improve with maturity, but eventually kidneys fail

Liver involvement: congenital hepatic fibrosis and dilation of hepatic bile ducts

Medullary Sponge Kidney

Congenital multiple cystic dilations of the collecting ducts in the medulla

Increased risk of renal calculi, urinary tract infection, and mild hematuria

Incidental finding on radiology

Nephronophthisis

Rare autosomal recessive genetic disorder caused by NPHP mutation → dysfunctional primary cilia (ciliopathy)

Can be sporadic (nonfamilial); familial (juvenile nephronophthisis); or part of a larger genetic syndrome

Variable number of small cysts in the medulla, usually concentrated at the corticomedullary junction

Progressive tubular atrophy involving medulla and cortex and interstitial fibrosis

May present with polyuria and polydipsia and progress to ESRD in childhood and adolescence

Multicystic Renal Dysplasia

Multicystic Renal Dysplasia

Multicystic Renal Dysplasia

Sporadic, congenital maldevelopment of one (more common) or both kidneys

Kidney replaced by cysts of variable size separated by undifferentiated mesenchyme often with cartilage and immature collecting ducts

Kidney will eventually involute

Associated with agenesis or atresia of ureter

Acquired Cystic Disease

Acquired Cystic Disease

ESRD patients with prolonged dialysis

Small cysts

lined by either hyperplastic or flattened tubular epithelium

Often contain calcium oxalate crystals

Generally asymptomatic, but sometimes cysts bleed, causing hematuria

100-fold increased risk of renal cell carcinoma

Nephrosclerosis

A. Globally sclerotic glomeruli

B. Shrunken glomeruli

C. Tubular atrophy

Nephrosclerosis

Renal pathology associated with sclerosis of renal arterioles and small arteries

Strongly associated with hypertension and diabetes

Hyaline arteriolosclerosis in response to hypertension, decreases blood flow to glomerulus

Micro vascular damage in diabetes contributes to decreased blood flow

Vascular disease leads to local ischemia, glomerulosclerosis and chronic tubulointerstitial injury

Gradual loss of kidney function, reduced kidney size and granular gross appearance

Common cause of ESRD

Acute Hypertensive Nephrosclerosis

Acute Hypertensive Nephrosclerosis

Acute Hypertensive Nephrosclerosis

High blood pressure (SP >180) causing end organ damage to the kidneys

“Onion skinning” of small renal arterioles

Causes acute or chronic kidney injury

Kidney injury contributes to worsening hypertension via increased Renin

Antihypertensive therapy may transiently worsen renal blood flow and reduce GFR

May require dialysis

Renal Artery Disease

Atherosclerosis or fibromuscular dysplasia of one or both renal arteries

Juxtaglomerular cells produce renin in response to decreased blood flow (stretch receptor) increasing blood pressure

Treatable with ACE or ARB blockade or reversible with stenting

Bilateral renal artery stenosis due to atherosclerosis is a reversible cause of CKD

Kidneys have no collateral circulation and are susceptible to thromboembolic disease

thrombotic microangiopathies

Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS) → thrombi in capillaries and arterioles (including renal arterioles)

Thrombi partially obstruct arterioles and shear red cells (schistocytes) leading to microangiopathic hemolytic anemia (MAHA)

Free Hemoglobin may cause direct damage to renal tubules

Thrombi in arterioles cases local necrosis and damages tubules and glomeruli

Can progress to renal failure

Sickle Cell Nephropathy

HbS crystalizes in response to hypoxia, oxidative stress or dehydration

The renal medulla is hypertonic causing dehydration of cells pushing HbS molecules closer together in a hypoxic environment leading to sickling

Hematuria and a diminished concentrating ability (hyposthenuria)

Patchy papillary necrosis

Proteinuria is common in sickle cell disease