Dialysis and Transplantation

Causes of ESRD by mechanism

• Metabolic/microvascular: Diabetic nephropathy is the single leading cause of ESRD in the United States (USRDS registry data); hyperglycemia drives glomerular hyperfiltration, mesangial matrix expansion, and Kimmelstiel-Wilson nodules
• Vascular: Hypertensive nephrosclerosis is the second leading cause; chronic pressure injury produces arteriolar hyalinosis and global glomerulosclerosis. Renovascular disease and atheroembolic disease act by chronic ischemia
• Glomerular: FSGS, IgA nephropathy, membranous nephropathy, and lupus nephritis — podocyte injury and immune-complex deposition with persistent proteinuria as the common final pathway
• Tubulointerstitial: Chronic NSAID/analgesic exposure, lithium, calcineurin inhibitors, and myeloma cast nephropathy; fibrosis rather than glomerular loss dominates
• Cystic/genetic: ADPKD (progressive cyst expansion compressing parenchyma), Alport syndrome (type IV collagen defect)
• Obstructive: BPH, stones, retroperitoneal fibrosis — back-pressure atrophy, potentially reversible if relieved early
• Incomplete recovery from AKI, particularly after prolonged ATN or cardiac surgery

Non-modifiable risk factors

• Older age, male sex, family history of kidney disease, low birth weight/reduced nephron mass, and prior AKI episodes
• African ancestry: APOL1 high-risk variants markedly accelerate progression in FSGS and hypertension-attributed kidney disease — a classic stem detail

Modifiable risk factors (KDIGO CKD guidance)

• Poor glycemic control, uncontrolled blood pressure, and above all albuminuria, the strongest modifiable predictor of progression; RAAS blockade and SGLT2 inhibitors slow decline
• Smoking, obesity, repeated nephrotoxin exposure (NSAIDs, aminoglycosides, iodinated contrast)

Risk factors for RRT-specific failure

• Access: small/scarred veins, prior central catheters (subclavian stenosis), diabetes, and obesity predict fistula non-maturation (KDOQI vascular access guidance)
• Graft loss: HLA mismatch, high panel-reactive antibody from prior transfusions/pregnancies/re-transplant, prolonged cold ischemia, deceased vs living donor, and medication nonadherence

Mechanism of Dialysis

• Diffusion: Movement of solutes (urea, creatinine, potassium, phosphate) down a concentration gradient across a semipermeable membrane; drives clearance of small molecules
• Ultrafiltration: Convective removal of fluid and solutes via hydrostatic pressure gradient; essential for volume control and removal of larger uremic toxins
• Osmosis: Movement of water across the membrane in response to osmotic gradients created by dextrose or icodextrin in peritoneal dialysate
• Dialysate composition is manipulated (varying potassium, calcium, glucose) to restore electrolyte balance and remove excess fluid

Mechanism of Transplantation

• Immunologic tolerance or immunosuppression: Transplanted kidney functions through native glomerular and tubular mechanisms; requires pharmacologic suppression of T-cell and B-cell mediated rejection
• Restoration of native renal function: GFR recovery depends on donor quality, surgical technique, and absence of rejection; living donor kidneys typically recover faster than deceased donor kidneys
• Vascular anastomosis and ureteral reimplantation: Surgical creation of blood supply and drainage permits immediate perfusion; delayed graft function may occur despite technical success due to ischemia-reperfusion injury

Dialysis Indications and Timing

• Symptomatic uremia: Pericarditis, encephalopathy, nausea/vomiting unresponsive to medical management; indicates urgent need for initiation
• Fluid overload refractory to diuretics: Pulmonary edema, hypertension, or clinical signs of volume overload despite maximum tolerated diuretic doses
• Electrolyte abnormalities: Severe hyperkalemia (>6.5 mEq/L with ECG changes), metabolic acidosis (pH <7.2), or hypocalcemia uncontrolled by medical therapy
• Progressive decline in renal function: GFR <15 mL/min/1.73m² or clinical judgment; earlier initiation may be considered with protein malnutrition or hepatic disease
• Initiation without specific biochemical threshold may be appropriate in symptomatic patients or those with significant residual renal function loss

Transplant Candidate Presentation

• Medically stable ESRD patients on dialysis or with pre-emptive transplantation (before dialysis initiation, ideally from living donors)
• Variable presentation: Many are asymptomatic during the transplant evaluation process; assessment occurs in the outpatient setting
• Post-transplant changes: Improved energy, appetite, and cognitive function; reduced dietary restrictions and improved quality of life compared to dialysis

Dialysis Need Assessment

• Estimated glomerular filtration rate (eGFR): Calculated using KDIGO equations; <15 mL/min/1.73m² is standard threshold, though symptomatic patients may need earlier initiation
• Residual renal function (RRF): Measured by 24-hour urine collection and averaged with creatinine clearance; guides dialysis prescription intensity
• Uremic symptoms and signs: Clinical assessment for nausea, pruritus, cognitive changes, pericarditis, or fluid overload
• Laboratory markers: Serum creatinine, BUN (>100 mg/dL often prompts initiation), potassium, phosphate, albumin, and hematocrit
• Vascular access assessment: Evaluation for adequacy of dialysis delivery via ultrasound of native fistula or graft

Transplant Candidacy Assessment

• Serologic testing: ABO blood typing, HLA typing (to define incompatible combinations and calculate panel-reactive antibody [PRA] percentage), infectious disease screening (HIV, hepatitis B/C, CMV, EBV), and crossmatching
• Cardiovascular evaluation: Stress testing, echocardiography, and coronary angiography based on age and risk factors; cardiac clearance is mandatory before listing
• Cancer screening: Age-appropriate malignancy screening; certain active cancers are absolute contraindications
• Immunologic compatibility: Negative crossmatch (donor-specific antibodies absent) is required for deceased donor transplants; living donor incompatible transplants possible with desensitization protocols
• Psychosocial evaluation: Assessment of medication adherence, social support, and understanding of lifelong immunosuppression

Hemodialysis (HD)

• Vascular access creation: Arteriovenous (AV) fistula (preferred; requires 6-12 weeks maturation), AV graft (synthetic; quicker but higher infection risk), or central venous catheter (CVC) (temporary; higher infection and thrombosis risk)
• Standard prescription: 3-4 sessions per week, 4-5 hours per session; dialysate flow 500-800 mL/min; blood flow 300-400 mL/min in mature fistulas
• Adequacy monitoring: Kt/V >1.2 (where K = dialyzer clearance, t = session time, V = distribution volume of urea) or URR (urea reduction ratio) >65%
• Anticoagulation: Unfractionated heparin (UFH) most common (5000 unit bolus, then 1000-2000 unit/hr drip); low-molecular-weight heparin (LMWH) or fondaparinux alternatives; direct thrombin inhibitors for heparin-induced thrombocytopenia (HIT)
• Electrolyte management: Individualized dialysate potassium (typically 2-3 mEq/L) and calcium concentration; phosphate removal by dialysis plus dietary restriction and phosphate binders

Peritoneal Dialysis (PD)

• Continuous ambulatory peritoneal dialysis (CAPD): 4 exchanges daily, 2-3 liters per exchange; patient performs manual exchanges
• Automated peritoneal dialysis (APD): Machine-driven nocturnal or nightly intermittent exchanges; improved phosphate and middle-molecule clearance
• Dialysate composition: Dextrose (1.5%, 2.5%, 4.25%) creates osmotic gradient; icodextrin alternative for long dwell exchanges
• Adequacy: Kt/V >1.7 (higher requirement than HD due to incomplete clearance); peritoneal equilibration test (PET) guides prescription
• Catheter care: Tenckhoff catheter or coiled varieties; exit site and tunnel care essential to prevent infections
• Advantages: Greater residual renal function preservation, cardiovascular stability, dietary flexibility, and independence
• Disadvantages: Risk of peritonitis (treated with intraperitoneal antibiotics), peritoneal sclerosis with long-term use, weight gain from glucose absorption, and contraindication with extensive abdominal surgery or adhesions

Kidney Transplantation

• Immunosuppressive regimen (induction and maintenance):
• Induction therapy: Basiliximab (anti-CD25 antibody) or anti-thymocyte globulin (ATG) for high-risk recipients; reduces acute rejection risk
• Maintenance therapy: Triple agent regimen most common—calcineurin inhibitor (tacrolimus preferred over cyclosporine due to better outcomes), mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), and corticosteroids (variable tapering protocols)
• Alternative regimens: **mTOR inhibitors (sirol

Hemodialysis complications

• Intradialytic hypotension: most common acute complication; ultrafiltration outpaces plasma refill. Signals: cramps, yawning, nausea mid-session. Management is reducing the ultrafiltration rate and reassessing dry weight
• Dialysis disequilibrium syndrome: rapid urea clearance leaves brain osmoles behind → water shifts intracellularly → cerebral edema. Headache, confusion, seizures in a first-ever session — an emergency; prevent with short, low-efficiency initial treatments
• Access thrombosis/stenosis: loss of thrill and bruit, prolonged post-needle bleeding, rising venous pressures → urgent fistulogram
• Dialysis access steal syndrome: shunting distal to the anastomosis causes a cold, painful, pale hand
• High-output heart failure: large fistula shunts markedly increase cardiac output (positive Nicoladoni-Branham sign)
• Access hemorrhage from a ruptured aneurysm and catheter-related bacteremia (usually Staphylococcus aureus) are emergencies; the latter risks endocarditis and epidural abscess. Blood cultures from catheter and periphery, then empiric vancomycin — dosed to a 24-hour AUC/MIC of 400–600 per the 2020 IDSA/ASHP consensus, not a trough target — plus gram-negative coverage
• Dialysis-related amyloidosis: β2-microglobulin is poorly cleared → carpal tunnel syndrome, shoulder arthropathy, cystic bone lesions after years on dialysis

Peritoneal dialysis complications

• Peritonitis: cloudy effluent with abdominal pain; diagnosis by effluent cell count (neutrophil-predominant leukocytosis), Gram stain, and culture, with intraperitoneal antibiotics per ISPD guidance
• Encapsulating peritoneal sclerosis, hernias, glucose absorption with hyperglycemia and weight gain

Transplant complications

• Hyperacute rejection: preformed anti-HLA/ABO antibodies → intraoperative graft mottling and thrombosis; emergency graft nephrectomy, no salvage
• Acute cellular rejection: T-cell tubulitis on biopsy → pulse corticosteroids; antibody-mediated rejection: donor-specific antibodies with peritubular capillary C4d staining
• Calcineurin inhibitor toxicity: afferent arteriolar vasoconstriction; tacrolimus adds tremor, post-transplant diabetes, hyperkalemia, hypomagnesemia
• Infection and malignancy: CMV and BK polyomavirus, Pneumocystis, EBV-driven PTLD, and squamous cell skin cancer

• Diabetes then hypertension are the top two causes of ESRD in the US; a stem with long-standing type 2 diabetes, albuminuria, and retinopathy needs no biopsy
• Access hierarchy is fistula > graft > catheter (KDOQI): fistulas last longest and infect least but need weeks to mature; catheters carry the highest bacteremia risk. Protect the nondominant arm — no BP cuffs, IVs, or PICCs — and avoid subclavian catheters, which cause central venous stenosis that later dooms an ipsilateral fistula
• Cloudy peritoneal effluent is peritonitis until proven otherwise. Single best next step: send effluent for cell count, Gram stain, and culture, then give intraperitoneal antibiotics (ISPD). Common distractor: pulling the catheter first — catheters are usually salvaged unless there is refractory, relapsing, or fungal infection
• Carpal tunnel syndrome plus shoulder pain in a long-term hemodialysis patient = β2-microglobulin (dialysis-related) amyloidosis, an AL/AA-distinct amyloid subtype
• Tacrolimus vs cyclosporine: gingival hyperplasia and hirsutism belong to cyclosporine; tacrolimus gives neurotoxicity (tremor), new-onset diabetes after transplant, hyperkalemia, and hypomagnesemia. Both are nephrotoxic through afferent arteriolar vasoconstriction — a rising creatinine may be drug toxicity, not rejection, so check a trough level and biopsy before escalating immunosuppression
• Azole antifungals, macrolides, and diltiazem inhibit CYP3A4 and spike tacrolimus levels; rifampin does the opposite. This is the classic drug-interaction item
• BK polyomavirus nephropathy: creeping creatinine months after transplant, decoy cells in urine, SV40-positive biopsy. Treatment is reducing immunosuppression, not adding an antiviral — the most common wrong answer
• Timing separates rejection types: minutes (hyperacute, preformed antibodies, graft nephrectomy) vs days-to-months (acute cellular, pulse steroids) vs years (chronic allograft injury with interstitial fibrosis/tubular atrophy, largely irreversible). Squamous cell skin cancer is the most common post-transplant malignancy — annual dermatologic surveillance and sun protection per KDIGO transplant recipient guidance