Congenital kidney conditions Notes

NOTES NOTES CONGENITAL KIDNEY CONDITIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES DIAGNOSIS ▪ Kidney abnormalities present at birth ▪ Polycystic kidney disease, multicystic dysplastic kidney, horseshoe kidney, renal agenesis DIAGNOSTIC IMAGING Developmental phases ▪ Pronephros → mesonephros → migrate upwards into abdomen → separate into two kidneys LAB RESULTS COMPLICATIONS OTHER DIAGNOSTICS ▪ Progressive renal damage, renal failure Ultrasound, CT scan, intravenous urethrogram, MRI ▪ Evaluate renal function; blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), serum electrolytes ▪ Visible at birth: bladder exstrophy, hypospadias, epispadias RISK FACTORS ▪ More common in individuals who are biologically male ▪ Pregnancy: high BMI, alcohol abuse, smoking, teratogenic medication ▪ Genetics SIGNS & SYMPTOMS ▪ Potter sequence (epicanthal folds, low-set ears, flat nose, recessed chin) TREATMENT MEDICATIONS ▪ Support renal function ▫ Diuretics, erythropoietin (EPO), medication for electrolyte imbalances, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers SURGERY ▪ Kidney transplant OTHER INTERVENTIONS Dialysis ▪ If kidney(s) no longer functional, machine performs kidney function; filtering, purifying blood by removing waste, excess fluid OSMOSIS.ORG 783

HORSESHOE KIDNEY osms.it/horseshoe-kidney PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ AKA renal fusion, congenital disorder; two kidneys fuse during fetal development → one large, horseshoe-shaped kidney ▪ Week 7–8 ▫ Horseshoe-shaped kidney tries to migrate from pelvis up into abdomen → gets hooked around inferior mesenteric artery → remains low in abdomen ▪ Mostly asymptomatic, sweating, nausea, vomiting; hematuria; fever, chills; cloudy urine CAUSES DIAGNOSTIC IMAGING Mechanical fusion ▪ Metanephros stage (gestation week 5) ▪ Flexion/growth of developing spine, pelvic organs → pushes kidneys together → lower poles of kidneys fuse → fibrous isthmus forms ▫ Isthmus made of connective tissue Ultrasound ▪ Periodic monitoring for early Wilms’ tumor detection Teratogenic event ▪ Posterior nephrogenic cells (help form part of kidney) migrate to wrong spot → parenchymal isthmus forms → connects kidneys ▫ Isthmus made of kidney cells RISK FACTORS ▪ More common in individuals who are biologically male ▪ Chromosomal disorders (e.g. Turner syndrome, trisomy 13, 18, 21) ▪ Neural tube defects COMPLICATIONS ▪ Hydronephrosis, kidney stones, infection, kidney cancer (especially Wilms’ tumor, carcinoid tumor), obstruction, vesicoureteral reflux, infection, polycystic kidney disease 784 OSMOSIS.ORG DIAGNOSIS ▪ Usually incidental CT scan ▪ 3D scanning: evaluate anatomy, collecting system MRI ▪ Provide anatomical information ▪ Evaluate arterial anatomy before surgery ▪ Check renal artery stenosis in hypertensive people LAB RESULTS ▪ BUN, creatinine, glomerular filtration rate (GFR), serum studies, 24-hour kidney stone risk assessment TREATMENT MEDICATIONS ▪ For renal disease (e.g. erythropoietin, ACE inhibitors) SURGERY ▪ Possibly corrective surgery

Chapter 110 Congenital Kidney Conditions Figure 110.1 An abdominal CT scan in the axial plane demonstrating a horseshoe kidney. There is renal tissue connecting the right and left kidneys. Figure 110.2 A 3D-reconstruction MRI in an anterior view in an individual with a horseshoe kidney. MEDULLARY CYSTIC KIDNEY DISEASE (MCKD) osms.it/mdullary-cystic-kidney-disease PATHOLOGY & CAUSES ▪ A group of autosomal dominant kidney diseases that cause progressive renal failure ▪ AKA autosomal dominant tubulointerstitial kidney disease (ADTKD) TYPES Uromodulin kidney disease (UKD) ▪ Caused by UMOD gene mutations ▪ Encodes uromodulin (Tamm–Horsfall protein), a non-ciliary protein ▫ Maintains integrity of the thick ascending limb of the loop of Henle ▪ Intracellular abnormal uromodulin accumulation → tubular cell atrophy → progressive renal failure + ↓ urate excretion → hyperuricemia, gout ADTKD due to REN mutations: REN (ADTKD-REN) ▪ Caused by REN gene mutations ▪ Encodes renin, a key hormone in the RAAS pathway ▪ Intracellular pre-prorenin accumulation → structural damage, apoptosis of reninproducing cells → progressive renal failure + ↓ renin production → ↓ blood pressure, anemia Mucin-1 kidney disease (MKD) ▪ Caused by MUC1 gene mutations ▪ Encodes mucin-1 ▪ Pathophysiology not completely understood; results in progressive renal failure OSMOSIS.ORG 785

COMPLICATIONS ▪ Gout, chronic kidney disease, end-stage renal disease (ESRD), low blood pressure, anemia SIGNS & SYMPTOMS ▪ Clinical manifestations of chronic kidney disease UKD ▪ Gout occurs at early age ADTKD-REN ▪ Low/low-normal blood pressures, anemia (occurs in childhood; resolves in adolescence from the influence of sex hormones), mild hyperkalemia MKD ▪ ↑ serum creatinine, hyperuricemia and gout occurring later in life DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound ▪ Small to normal kidneys with occasional cysts UKD (presumptive diagnosis factors) ▪ All three of the following ▫ Strong family history of kidney disease ▫ Family history of gout ▫ Urinalysis: bland urinary sediment; absence of proteinuria or hematuria ADKTD-REN (presumptive diagnosis factors) ▪ Family history of chronic kidney disease, plus one of the following ▪ Unexplained anemia out of proportion to ↓ glomerular filtration rate ▪ Evidence of acute kidney injury; bland urinary sediment ▪ Chronic kidney disease + hyperkalemia, low or low-normal blood pressure, and hyperuricemia MKD (presumptive diagnosis factors) ▪ Presentation chronic kidney disease plus each of the following findings ▫ Urinalysis: bland urinary sediment; little or no proteinuria ▫ Absence of symptoms associated with UKD (precocious gout) or ADKTD-REN (childhood anemia, hyperkalemia, and hyperuricemia) TREATMENT LAB RESULTS MEDICATIONS Urinalysis ▪ See presumptive diagnosis factors for each subtype UKD ▪ Gout: allopurinol Biopsy ▪ Interstitial fibrosis OTHER DIAGNOSTICS ▪ Confirmed through genetic testing ADTKD-REN ▪ Symptomatic anemia: erythropoietin ▪ Low blood pressure, hyperkalemia: fludrocortisone ▪ Avoid NSAIDs SURGERY ▪ Treat progressive renal failure; kidney transplantation 786 OSMOSIS.ORG

Chapter 110 Congenital Kidney Conditions MEDULLARY SPONGE KIDNEY (MSK) osms.it/medullary-sponge-kidney PATHOLOGY & CAUSES ▪ Rare congenital disorder characterized by ectasia (dilation) of the renal collecting ducts ▪ Genetic basis for developmental abnormality is incompletely understood; may involve embryonic disruption of the ureteral-bud and the metanephric blastema ▪ Renal collecting duct dilation, distension → urinary stasis → medullary cyst formation → impaired acidification in the terminal collecting duct → ↑ urine pH → nephrocalcinosis RISK FACTORS ▪ Associated conditions include hemihypertrophy, Beckwith–Wiedemann syndrome COMPLICATIONS ▪ Urinary tract infections ▪ Nephrocalcinosis ▪ Renal calculi (calcium phosphate, calcium oxalate) ▪ Chronic kidney disease SIGNS & SYMPTOMS DIAGNOSIS ▪ Often discovered incidentally during investigations for another indication DIAGNOSTIC IMAGING Intravenous pyelography ▪ Cystic dilatations have brushlike appearance; enlarged pyramids; clusters of stones CT scan ▪ Medullary nephrocalcinosis LAB RESULTS ▪ Hypercalciuria, hyperuricosuria, hypocitraturia, and hyperoxaluria TREATMENT MEDICATIONS Treat complications ▪ Urinary tract infection: antibiotics ▪ Recurrent stone formation: potassium citrate, thiazide diuretics, ↑ fluid intake, ↓ sodium in diet ▪ Often asymptomatic, flank pain, renal colic, hematuria, dysuria, nocturia OSMOSIS.ORG 787

Figure 110.3 An X-ray image of the kidney, ureters and bladder. The dilated collecting ducts of the nephron give a paintbrush effect to each renal calyx. MULTICYSTIC DYSPLASTIC KIDNEY (MCDK) osms.it/dysplastic-kidney PATHOLOGY & CAUSES ▪ Congenital disease, one/both kidneys do not form correctly → urine does not drain properly, builds up in kidneys, forms multiple fluid-filled sacs (cysts) ▪ Result of abnormal induction of metanephric blastema by ureteric bud ▫ Possibly due to malformation of mesonephric duct/ureteric bud/both ▪ Ureteric bud fails to produce ureters, renal calyces, collecting ducts, collecting tubules ▫ Urine cannot exit kidney, builds up → forms fluid-filled cysts ▫ Fluid-filled cysts composed of abnormal connective tissue replace normal kidney tissue → kidney function decreases CAUSES ▪ Mostly sporadic ▪ Potential link to medication during pregnancy ▫ ACE inhibitors, illicit drugs (e.g. cocaine) ▪ Without treatment → kidney involutes (shrinks due to inactivity) RISK FACTORS ▪ More common in individuals who are biologically male, genetic syndromes (papillorenal syndrome; error in genes EYA1, SIX1, PAX2) COMPLICATIONS Bilateral MCDK ▪ Potter sequence Unilateral MCDK ▪ Uncommon, risk of chronic kidney disease 788 OSMOSIS.ORG

Chapter 110 Congenital Kidney Conditions TREATMENT SIGNS & SYMPTOMS Unilateral MCDK ▪ Asymptomatic/palpable flank mass Bilateral MCDK ▪ Potter sequence DIAGNOSIS ▪ May go undiagnosed if unilateral, no palpable flank mass, remaining kidney compensating fully DIAGNOSTIC IMAGING Antenatal ultrasound ▪ Most common ▪ Visualize kidney containing multiple large, peripheral cysts Ultrasound ▪ Performed on neonate if health professionals detect palpable flank mass SURGERY Mild bilateral MCDK ▪ Dialysis, kidney transplant ▪ Newborn requires dialysis/kidney transplant OTHER INTERVENTIONS Unilateral MCDK ▪ Observation ▫ Affected kidney involutes ▪ Follow-up ▫ Serial ultrasound evaluation at birth, four weeks, two years, five years, 10 years of age; blood pressure, urinalysis (for proteinuria), renal function studies Severe bilateral MCDK ▪ Provide support for Potter sequence ▪ Newborns generally don’t survive Figure 110.4 Pathological features of multicystic dysplastic kidney. OSMOSIS.ORG 789

POLYCYSTIC KIDNEY DISEASE (PKD) osms.it/polycystic-kidney PATHOLOGY & CAUSES ▪ Genetic disease, kidneys fill with hundreds of cysts → become larger, unable to function ▪ Cysts in outer layer (cortex), inner layer (medulla) of kidneys ▪ Cysts lined with renal tubular epithelium, become larger ▪ Cysts make kidneys larger over time → compress blood vessels of neighboring healthy nephrons → starve neighboring nephrons of oxygen → poor perfusion of kidneys activates renin-angiotensinaldosterone system → retain fluid → hypertension ▪ Large cysts → compress collecting system → urinary stasis → kidney stones TYPES Autosomal dominant ▪ AKA adult PKD; usually manifests in adulthood ▪ Polycystin 1 (PKD1), polycystin 2 (PKD2) ▫ Necessary for inhibition of cell proliferation; if absent, cells proliferate abnormally, water moves to cyst lumen ▪ PKD1 gene mutation → more severe, earlier onset ▪ PKD2 gene mutation → less severe, later onset Autosomal recessive ▪ AKA infantile PKD; usually manifests in infancy ▫ Possible renal failure before birth → trouble producing urine → low amniotic 790 OSMOSIS.ORG fluid (oligohydramnios) ▪ Inherited mutation on both copies of polycystic kidney hepatic disease 1 (PKHD1) gene, fibrocystin protein ▫ Fibrocystin co-localizes with PKD2 regulation pathway, calcium signaling similar to autosomal dominant RISK FACTORS Autosomal dominant ▪ One parent passes along PKD1/PKD2 mutation Autosomal recessive ▪ Both parents pass along PKHD1 mutation COMPLICATIONS ▪ Renal insufficiency → renal failure ▪ Kidney stones Autosomal dominant ▪ Cerebral artery berry aneurysms ▪ Mitral valve prolapse ▪ Benign hepatic cysts ▪ Heart failure (due to aortic root dilation) Autosomal recessive ▪ Congenital hepatic fibrosis → portal hypertension ▪ Ascending cholangitis (due to obstructed biliary tree) SIGNS & SYMPTOMS ▪ Flank pain, high blood pressure, hematuria (blood in urine), renal insufficiency, renal failure, fetal oligohydramnios in autosomal recessive PKD

Chapter 110 Congenital Kidney Conditions DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound ▪ For autosomal recessive polycystic kidney disease ▪ Bilaterally large kidneys with cysts, oligohydramnios LAB RESULTS ▪ Complete blood count (CBC), urinalysis, urine culture TREATMENT MEDICATIONS ▪ Hypertension: ACE inhibitors, angiotensin receptor blockers ▪ Cholestasis: ursodiol (slows down rate of cholesterol absorption by intestines) SURGERY ▪ Kidney transplant Portal hypertension ▪ Portocaval shunt → bypasses liver, connects portal vein to inferior vena cava; liver transplant OTHER INTERVENTIONS ▪ Dialysis Figure 110.5 Histological appearance of renal parenchyma in a case of polycystic kidney disease. Figure 110.6 A CT scan in the coronal plane demonstrating innumerable cysts in the kidneys and liver in autosomal dominant polycystic kidney disease. Figure 110.7 The gross pathological appearance of polycystic kidneys. OSMOSIS.ORG 791

RENAL AGENESIS osms.it/renal-agenesis PATHOLOGY & CAUSES ▪ Ureteric bud fails to induce metanephric blastema to develop → one/both kidneys don’t form TYPES Unilateral renal agenesis (URA) ▪ One kidney does not develop ▫ Usually asymptomatic if other kidney healthy, able to compensate ▫ Predisposes individuals to more serious renal problems Bilateral renal agenesis (BRA) ▪ Neither kidney develops ▫ Incompatible with life outside womb ▫ Usually fatal within first few days after birth; no treatment SIGNS & SYMPTOMS ▪ Oligohydramnios/anhydramnios (no amniotic fluid) ▪ Symptoms at birth include high blood pressure, protein/blood in urine, swelling of face/extremities URA ▪ Bsually asymptomatic if other kidney healthy BRA ▪ Babies ill at birth, usually do not live ▫ Widely separated eyes with epicanthal folds ▫ Low set ears ▫ Flat, broad nose ▫ Small chin ▫ Underdeveloped lungs CAUSES ▪ Combination of genetic/in utero environmental factors (toxins, infections) RISK FACTORS ▪ More common in individuals who are biologically male COMPLICATIONS URA ▪ Hypertrophy of remaining kidney, infections, kidney stones, hypertension, renal failure BRA ▪ Oligohydramnios, pulmonary hypoplasia, Potter sequence 792 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound/MRI ▪ Confirm diagnosis OTHER DIAGNOSTICS ▪ Oligohydramnios/anhydramnios TREATMENT SURGERY ▪ Kidney transplant OTHER INTERVENTIONS ▪ Routine monitoring ▪ Dialysis

Chapter 110 Congenital Kidney Conditions Figure 110.8 A 3D reconstruction of a CT scan demonstrating left-sided renal agenesis. Figure 110.9 An MRI scan in the coronal plane demonstrating right-sided renal agenesis. OSMOSIS.ORG 793