Screening and Monitoring

1. Lipid management follows a “fire-and-forget” strategy. 4D, AURORA, and SHARP demonstrated no cardiovascular benefit from statin initiation in prevalent HD patients. KDIGO 2013/2024 recommends against initiation on dialysis while supporting continuation of pre-existing therapy [1-4].

2. HbA1c is systematically unreliable in HD. Shortened erythrocyte lifespan, ESA use, and carbamylated hemoglobin underestimate true glycemia by approximately 25 mg/dL. CGM is the gold standard; glycated albumin is the preferred lab alternative [5-9].

3. CKD-MBD monitoring follows KDIGO 2017 — but the EVOLVE trial (cinacalcet) failed its primary composite endpoint despite lowering PTH, and IMPROVE-CKD showed no vascular calcification benefit from phosphate binders. Phosphorus-mortality association is modified by albumin status; phosphorus variability predicts mortality independently [10,11,85,86,87,88].

4. Hepatitis, thyroid, cancer, ACKD screening — HCV every 6 months; TSH at initiation and annually (11-28% prevalence); cancer screening individualized by life expectancy; ACKD ultrasound beginning at 3 years of dialysis [12-24].

5. Fish oil supplementation is now recommended (Grade 2B) based on the PISCES trial (1,228 patients, 26 sites, 3.5-year follow-up; 4g omega-3 PUFAs daily — EPA 1.6g + DHA 0.8g vs corn-oil placebo; HR 0.57, 95% CI 0.47–0.70, p<0.001 for serious CV events; RRR 43%, ARR approximately 11%/year, NNT approximately 9/year) — the first positive CV prevention trial in dialysis since the three statin failures [25].

6. Depression (20-40%) and cognitive impairment (10-80%) are prevalent, undertreated, and treatment-modifying. PHQ-9 screening at initiation and annually [26-28].

Cardiovascular and Vascular Access Assessment

7. Echocardiography must include right heart assessment — and should be performed before vascular access creation. AV fistula-related high-output cardiac failure affects 29.4% of AVF patients when confirmed by RHC [65]. RV dilation post-AVF creation independently predicts mortality (HR 3.9, 95% CI 1.7–9.2) [62]. Access flows >1.5–2.0 L/min or Qa/CO >20–30% are strongly associated with LVH, pulmonary hypertension, and RV failure [55,64].

8. Vascular access selection must account for cardiac status. Upper arm AVF carries OR 8.1 for HOHF vs forearm [65]. Forearm AVF mean flow is 948 mL/min vs 1,580 mL/min for upper arm [67]. In patients with symptomatic heart failure, CVC demonstrated non-inferior major adverse event-free survival vs AVF [69]. A tiered approach based on EF and RV function — from forearm-first strategies through catheter for EF <15% — replaces the “fistula first at all costs” paradigm [52,53].

9. Flow reduction techniques (banding, RUDI, DRIL, small-diameter interposition, ligation) show 75–100% symptom resolution rates. Tapered grafts do not prevent HOHF (VQI n=3,608: HR 1.03) [70-75].

The Quality Metrics Critique

10. Kt/V does not improve mortality beyond a minimum floor. The HEMO trial (n=1,846, 7 years) showed no benefit from higher Kt/V. Meyer et al. (2016) demonstrated that higher Kt/V produced 0% reduction in p-cresyl sulfate and only 22% reduction in methylguanidine — the solutes Kt/V was supposed to represent are not cleared by increasing it [78,79].

11. Albumin is 21 times more powerful than URR as a mortality predictor (Owen 1993 [76]), and malnutrition on HD carries a pooled mortality HR of 1.53 (29 studies, 11,063 patients) [46]. But albumin is driven primarily by inflammation, not nutrition — declines correlate with CRP and IL-6, not with protein intake (nPCR) [89-91]. Low albumin predicts mortality only when accompanied by elevated CRP [92,93]. CRP must accompany every albumin measurement.

12. The pattern repeats across every major quality metric. Hemoglobin: CHOIR, CREATE, and TREAT showed ESA-driven normalization increases mortality [82-84]. Phosphorus: no binder has demonstrated mortality benefit (IMPROVE-CKD negative) [85]. PTH: EVOLVE failed [86]. The consistent finding is that fixing the number does not fix the patient.

The Path Forward: High-Volume Hemodiafiltration

13. HDF addresses what Kt/V cannot. ESHOL (2013): 30% all-cause mortality reduction. CONVINCE (2023): 23% all-cause mortality reduction at convective volumes ≥23 L/session [94,95]. CONTRAST demonstrated that CRP and IL-6 rise on conventional HD but remain stable on HDF (approximately 20% per year difference) [96]. HDF clears middle molecules by convection — the toxin class that Kt/V misses entirely. The relevant dose metric is convective volume, not Kt/V.

1.1 The Lipid Paradox in Dialysis

The dyslipidemia profile in HD patients is not the dyslipidemia that statins were designed to treat. Elevated triglycerides, low HDL-cholesterol, and relatively modest LDL elevations characterize the uremic lipid phenotype — driven by decreased lipoprotein lipase and hepatic lipase activity, apolipoprotein C-III enrichment of circulating lipoproteins, and impaired clearance of triglyceride-rich remnant particles [30].

The paradox runs deeper. Lower total cholesterol in HD patients is associated with increased mortality — the “reverse epidemiology” phenomenon reflecting the confounding influence of malnutrition, chronic inflammation, and protein-energy wasting. The malnutrition-inflammation-cachexia syndrome (MICS) drives down cholesterol while simultaneously driving up cardiovascular risk through pathways that statins cannot address [30,31].

1.2 KDIGO Lipid Guideline Recommendations

The KDIGO 2013 Clinical Practice Guideline for Lipid Management in CKD fundamentally changed the approach to lipid management in dialysis patients. The KDIGO 2024 CKD guideline explicitly endorses these 2013 recommendations without modification [3,4]:

• Obtain an initial lipid profile (total cholesterol, LDL, HDL, triglycerides) at CKD diagnosis and at dialysis initiation (1C)
• Do not initiate statin or statin/ezetimibe therapy in patients already on chronic dialysis (2A)
• Continue statin therapy in patients already taking statins at the time of dialysis initiation (2C)
• Follow-up lipid measurements are not routinely required — the guideline endorses a “fire-and-forget” approach, abandoning LDL targets in favor of risk-based prescribing (Not Graded)

1.3 Evidence Base: Why Statins Do Not Work in Dialysis

Three landmark trials established the lack of cardiovascular benefit of statins in prevalent HD patients. Each was adequately powered, well-conducted, and unambiguous:

The consistency across three trials, two statins, and over 7,000 dialysis patients leaves little room for ambiguity. LDL lowering works in early CKD. It does not work once patients reach dialysis.

1.4 Primary vs. Secondary Prevention: The Guideline-Practice Gap

The KDIGO 2013 recommendation against initiating statins in dialysis-dependent CKD (2A) does not distinguish between primary and secondary prevention. The evidence base supports this unified position: the 4D trial enrolled exclusively diabetic HD patients (a high-risk secondary prevention-equivalent population), and AURORA included patients ages 50-80 with substantial baseline cardiovascular disease burden. Neither demonstrated benefit even in subgroups with prior cardiovascular events [1,2].

In practice, however, a significant guideline-practice gap exists:

The discomfort with withholding statins for secondary prevention in dialysis reflects the tension between nephrology-specific evidence (4D, AURORA, SHARP dialysis subgroup — all negative) and cardiology practice guidelines (ACC/AHA 2018), which recommend high-intensity statin therapy for all patients with clinical ASCVD without carving out a dialysis exception. Most cardiologists will initiate a statin after an acute MI in a dialysis patient as part of standard post-ACS management, even though the nephrology evidence does not support benefit.

1.5 Lipid Monitoring: The “Fire-and-Forget” Approach

The “fire-and-forget” approach applies equally regardless of whether the patient is on a statin for primary or secondary prevention. KDIGO explicitly abandoned LDL targets in CKD, including dialysis. There is no LDL goal to titrate toward [3].

When to check lipids:

1.6 Fish Oil: The First Positive Cardiovascular Trial in Dialysis

In a field defined by three consecutive statin failures, the 2025 PISCES trial (Lok CE et al., NEJM 2025) represents a genuine practice-changing event. 1,228 maintenance hemodialysis patients across 26 sites in Canada and Australia were randomly assigned to 4g omega-3 PUFAs daily (EPA 1.6g + DHA 0.8g) versus corn-oil placebo and followed for 3.5 years. The primary endpoint — serious cardiovascular events (composite of cardiovascular death, nonfatal MI, nonfatal stroke, and peripheral vascular disease leading to amputation) — was significantly lower in the fish oil group (HR 0.57, 95% CI 0.47–0.70, p<0.001; event rates 0.31 versus 0.61 per 1,000 patient-days; RRR 43%, ARR approximately 11%/year, NNT approximately 9/year). The benefit extended to patients without prior CVD history [25].

UpToDate has updated its recommendation: fish oil supplementation is now suggested for all patients on maintenance dialysis (Grade 2B). This is the first positive pharmacologic intervention trial for cardiovascular event reduction specific to the dialysis population.

Section Summary

Lipid management in HD follows a “fire-and-forget” strategy with no routine monitoring after baseline. Three landmark trials (4D, AURORA, SHARP dialysis subgroup) established that statin initiation in prevalent dialysis patients provides no cardiovascular benefit, and KDIGO 2024 reaffirms this position. Continue statins started pre-dialysis. The PISCES trial (2025) represents the first positive CV prevention trial in dialysis, supporting fish oil supplementation for all maintenance HD patients (Grade 2B). Routine lipid panels in stable HD patients on statins are low-value care.

2.1 Why HbA1c Fails in Hemodialysis

HbA1c reflects average blood glucose over the 90-120 day erythrocyte lifespan. In HD patients, that lifespan is shortened to 60-90 days, and multiple additional factors conspire to make HbA1c unreliable [5-7]:

The net effect is typically underestimation. HbA1c systematically underestimates true glycemia in HD patients by approximately 1.4 mmol/L (25 mg/dL) of mean glucose [8]. This is not a subtle bias — it is a clinically meaningful gap that can lead to false reassurance about glycemic control.

2.2 What the Guidelines Say — And Where They Diverge

A tension exists between KDIGO’s 2022 position and the emerging CGM-era evidence:

KDIGO 2022 Diabetes in CKD Guideline: Recommends HbA1c as the “primary glycemic biomarker” even in dialysis patients, with monitoring twice yearly for stable patients meeting goals and quarterly for those with therapy changes or unmet targets. KDIGO acknowledges that accuracy and precision decline in advanced CKD but argues that glycated albumin and fructosamine “offer no known advantages over HbA1c” and are biased by hypoalbuminemia [33].

ADA/KDIGO 2022 Consensus Report: Emphasizes concurrent use of CGM when HbA1c may be inaccurate or when assessing hypoglycemia risk. The consensus acknowledges that “neither glycated albumin nor fructosamine is without limitations” but stops short of replacing HbA1c as the primary marker [34].

2024 JDST Consensus on CGM in CKD: A more assertive position — recognizes that in patients with ESKD and “burnt-out diabetes,” CGM is superior to HbA1c for detecting occult hyperglycemia and hypoglycemia. Recommends CGM as part of standard glycemic management in dialysis patients with diabetes [35].

Zelnick 2026 Diabetes Care (Prospective Study): The most recent and methodologically rigorous data. A prospective study using CGM in maintenance dialysis patients confirmed that both HbA1c and glycated albumin correlate strongly with CGM-derived mean glucose (r = 0.85 and 0.87, respectively), but each has substantial bias from clinical characteristics — ESA dose, hemoglobin level, albumin concentration, BMI, and dialysis modality all independently distort both markers [36].

The bottom line: no single lab test is reliable in isolation. A multimodal approach is required.

2.3 The “Burnt-Out Diabetes” Phenomenon

Approximately 20% of diabetic ESKD patients have HbA1c values below 6.5% without antidiabetic therapy for more than 6 months — so-called “burnt-out diabetes” [9]. The 2024 Kaminski study in Diabetes Care used CGM (Dexcom G6) to evaluate these patients and demonstrated that:

• Burnt-out diabetes patients actually have significantly higher mean daily glucose than non-diabetic ESKD controls
• More frequent hyperglycemic episodes above 180 mg/dL
• Greater glycemic variability (higher coefficient of variation)

The apparent “remission” is largely an artifact of HbA1c unreliability in ESKD. These patients are not in remission. They are undertreated.

2.4 Alternative Glycemic Markers

Glycated Albumin (GA): - Reflects average glycemia over 2-3 weeks (albumin half-life approximately 20 days) - Unaffected by RBC lifespan, ESA use, or hemoglobin variants - Meta-analysis data demonstrate superior correlation with average glucose (R = 0.61) compared to HbA1c (R = 0.53) in CKD/dialysis patients [37] - Performs best among all glycemic markers in HD patients in head-to-head CGM comparisons [9] - Limitation: Affected by conditions altering albumin metabolism — nephrotic syndrome, cirrhosis, peritoneal dialysis protein losses, severe malnutrition. The 2026 Zelnick study confirmed albumin level independently biases GA [36]

Fructosamine: - Measures glycation of all serum proteins (predominantly albumin) - Reflects glycemia over 2-3 weeks - Less specific than glycated albumin; affected by albumin levels and protein turnover - The 2024 Kaminski study found fructosamine was not superior to HbA1c for glycemic assessment in ESKD — a significant finding that has cooled enthusiasm for this marker [9]

Continuous Glucose Monitoring (CGM): - Gold standard for real-time glycemic assessment in HD patients - Captures glycemic variability, time in range (TIR), time above range (TAR), time below range (TBR), and hypoglycemic episodes that no single lab marker can detect - Dexcom G6/G7 and Libre 2/3 are validated options in dialysis populations - Particularly valuable in detecting occult hyperglycemia in burnt-out diabetes - Increasingly incorporated into clinical practice; the 2024 JDST consensus report recommends CGM as a standard component of diabetes management in dialysis [35] - Practical limitation: Insurance coverage remains inconsistent for dialysis patients not on intensive insulin therapy. Cost is a barrier.

2.5 Glycemic Targets in ESKD

KDIGO 2022 recommends an individualized HbA1c target, generally in the range of 6.5-8.0%, but acknowledges that HbA1c may not accurately reflect glycemia in this population. The ADA/KDIGO 2022 consensus suggests relaxing targets in patients at high risk of hypoglycemia, with limited life expectancy, or with significant comorbidities [33,34].

For CGM-based targets, the 2024 JDST consensus recommends:

Section Summary

HbA1c systematically underestimates glycemia in HD patients due to shortened RBC lifespan, ESA use, and uremic effects — by approximately 25 mg/dL of mean glucose. Glycated albumin is the preferred lab alternative, but it too carries bias from albumin levels. CGM is the gold standard, capturing the glycemic variability and occult hyperglycemia that lab markers miss entirely. The “burnt-out diabetes” phenomenon is an artifact of HbA1c failure, not true remission. A multimodal approach — GA for trending, CGM for real-time management, HbA1c only with appropriate caveats — is the evidence-based standard.

3.1 KDIGO 2017 CKD-MBD Monitoring Recommendations

The KDIGO 2017 Guideline Update establishes the following monitoring schedule for CKD G5D patients [10]:

A 2026 narrative review in BMC Nephrology comparing international guidelines (KDIGO, KDOQI, ERA-EDTA, CSN) found no true consensus on optimal testing frequency, though all guidelines agree on the core parameters. The variation lies in recommended intervals and target ranges [38].

3.2 PTH Targets and Interpretation

For patients on dialysis, KDIGO recommends maintaining PTH levels within approximately 2-9 times the upper limit of normal for the assay [10]. This is a wide range — deliberately so. The variability in skeletal responsiveness to PTH in ESKD is enormous, influenced by:

• Duration of dialysis and prior parathyroid exposure
• Degree of hyperphosphatemia and calcium-phosphorus product
• Uremic toxin burden and chronic inflammation
• Skeletal resistance to PTH (a hallmark of uremic osteodystrophy)
• Vitamin D status and therapy

The 2024 KDIGO Controversies Conference acknowledged that PTH levels within this range represent a “gray zone” where standalone values are unreliable for predicting underlying bone histology. Bone biopsy remains the gold standard for diagnosing specific subtypes of renal osteodystrophy (high-turnover, low-turnover, mixed, osteomalacia), but it is rarely performed in clinical practice [11].

3.3 Phosphorus Management: The Evidence Gap

Hyperphosphatemia is associated with vascular calcification, cardiovascular events, and mortality in observational studies. The association is robust and consistent across cohorts. What is less clear is whether lowering phosphorus — particularly with phosphate binders — improves outcomes. No randomized trial has demonstrated that phosphate binder therapy reduces mortality in dialysis patients. The KDIGO 2017 guideline recommends lowering elevated phosphorus “toward the normal range” (2C) while acknowledging the limited interventional evidence [10].

3.4 Vitamin D

Vitamin D deficiency is nearly universal in ESKD. KDIGO recommends measuring 25(OH) vitamin D at dialysis initiation and correcting deficiency using strategies based on general population guidelines. Whether nutritional vitamin D supplementation (cholecalciferol or ergocalciferol) improves clinical outcomes in dialysis beyond correcting the lab value remains uncertain [10].

Active vitamin D analogues (calcitriol, paricalcitol, doxercalciferol) are used to manage secondary hyperparathyroidism. Their role in bone and cardiovascular outcomes continues to be debated.

Section Summary

CKD-MBD monitoring in HD patients follows KDIGO 2017 guidelines: calcium and phosphorus every 1-3 months, PTH every 3-6 months, ALP annually, and vitamin D at initiation. PTH should be maintained at 2-9 times the upper limit of normal, but trends matter far more than individual values. No RCT has shown that phosphate binder therapy reduces mortality. The 2024 KDIGO Controversies Conference reinforced that bone biopsy remains the only definitive diagnostic tool for renal osteodystrophy subtypes, but clinical management is guided by biochemical trends in the vast majority of patients.

4.1 Hepatitis C Virus (HCV)

HD patients are at increased risk of HCV acquisition through nosocomial transmission in dialysis units. Approximately 7-8% of chronic HD patients in the US are HCV seropositive, though rates have declined with improved infection control and universal precautions [12].

KDIGO 2022 Clinical Practice Guideline for Hepatitis C in CKD [12]:

The advent of direct-acting antivirals (DAAs) has transformed HCV management in CKD. Glecaprevir/pibrentasvir (Mavyret) is approved for all CKD stages including dialysis and achieves sustained virologic response (SVR) rates exceeding 98% in ESKD populations. HCV cure before transplant improves post-transplant outcomes and expands the donor pool — HCV-positive organs can be considered for HCV-negative recipients with peri-transplant DAA treatment [12].

4.2 Hepatitis B Virus (HBV)

HD patients have impaired humoral and cellular immune responses to HBV vaccination, making both screening and vaccination critical components of health maintenance.

CDC 2023 Recommendations [13]:

Vaccine considerations in dialysis:

Standard-dose hepatitis B vaccine produces adequate antibody response in only 50-60% of dialysis patients, compared to over 95% in the general population. High-dose formulations are recommended:

• Recombivax HB 40 mcg (double the standard dose) on a 0-, 1-, 6-month schedule — the traditional HD-specific regimen
• Heplisav-B (HBsAg with CpG 1018 adjuvant) — achieves higher seroprotection rates in the general population, but safety and effectiveness have not been specifically established in HD patients per the package insert [13]
• PreHevbrio (three-antigen vaccine) — similarly lacks HD-specific data [13]
• Nonresponders to the initial series should receive a second complete 3-dose series

Section Summary

Hepatitis screening in HD serves dual purposes — infection control and transplant planning. HCV screening every 6 months by immunoassay or NAT is KDIGO 1B, with DAA therapy now achieving >98% SVR even in ESKD. HBV screening at initiation with annual anti-HBs monitoring is essential given the impaired vaccine response in dialysis patients — only 50-60% achieve adequate antibody levels with standard dosing. High-dose hepatitis B vaccine formulations are recommended, and annual monitoring with revaccination at titers below 10 mIU/mL is the standard.

5.1 Prevalence and Clinical Significance

Hypothyroidism is significantly more prevalent in ESKD than in the general population. Reported rates range from 11% to 28% depending on the TSH threshold and population studied [14-17]:

A 2025 comprehensive review in Nature Reviews Endocrinology synthesized the relationship between kidney diseases and thyroid function, confirming that hypothyroidism in ESKD is not merely a laboratory curiosity [39]. Higher TSH levels are independently associated with:

• Coronary artery calcification in HD patients [17]
• Increased all-cause and cardiovascular mortality — a U-shaped relationship exists, with both low and high TSH associated with adverse outcomes [40]
• Left ventricular hypertrophy and diastolic dysfunction — exacerbating the already-prevalent cardiac structural disease in ESKD

5.2 Diagnostic Challenges

The symptoms of hypothyroidism overlap extensively with uremia — fatigue, cold intolerance, edema, constipation, dry skin, cognitive impairment, and weight gain are common to both conditions. Clinical diagnosis alone is unreliable. The diagnosis must be biochemical.

Low T3 syndrome (euthyroid sick syndrome) is common in ESKD and does not require treatment. It results from impaired peripheral conversion of T4 to T3, decreased TBG levels, and the catabolic/inflammatory milieu of chronic kidney disease. Low T3 is associated with worse outcomes in observational studies, but treatment trials have not demonstrated benefit — and thyroid hormone supplementation carries risk of atrial fibrillation and accelerated bone loss [39].

5.3 Thyroid Cancer Risk

An additional consideration: dialysis patients have an approximately 2.3-fold increased risk of thyroid cancer compared to the general population, though the absolute risk remains low. KDIGO does not issue a formal thyroid cancer screening recommendation. Clinical vigilance — thyroid palpation during routine exams, with ultrasonography if nodules are detected — is a reasonable approach [24,39].

5.4 Screening Recommendations

No formal guideline mandates thyroid screening in HD. However, given the high prevalence (11-28%), extensive symptom overlap with uremia (making clinical diagnosis impossible), and association with cardiovascular morbidity and mortality:

Recommended approach: - TSH at HD initiation — baseline assessment - TSH annually — surveillance - FT4 confirmation if TSH is abnormal - Do not check FT3 routinely — it is unreliable in ESKD and low T3 syndrome is common

Section Summary

Hypothyroidism affects 11-28% of HD patients — a prevalence that is 2-5 times higher than the general population. Its symptoms are indistinguishable from uremia, making clinical diagnosis impossible and laboratory screening essential. TSH is the most reliable test; FT3 and FT4 assays are unreliable in uremia. Higher TSH is independently associated with coronary calcification and mortality. TSH screening at HD initiation and annually thereafter is reasonable. Low T3 syndrome is common, associated with worse outcomes, but does not require treatment.

6.1 The Screening Dilemma

Cancer screening guidelines were developed for populations with decades of remaining life expectancy. The median survival of incident HD patients in the US is approximately 3-5 years, with wide heterogeneity based on age, diabetes status, comorbidities, and functional status. For a screening test to provide benefit, the lead time from detection to mortality reduction must fall within the patient’s expected survival window — typically 5-10 years for most cancers [18,19].

The ASN Choosing Wisely campaign explicitly recommends: “Don’t perform routine cancer screening for dialysis patients with limited life expectancies without signs or symptoms” [18].

A 2024 CJASN review — “Cancer Screening Among Patients with Kidney Failure Requiring Hemodialysis: Where We Are and Where We Are Going” — provides the most current framework for this decision space. The review highlights that general population screening guidelines are not directing care in HD, and nephrologists are increasingly wrestling with ownership of preventive care decisions in a population for whom those guidelines were never designed [20].

6.2 Individualized Framework

6.3 Cancer-Specific Considerations

Colorectal Cancer: - Third most common cancer in HD patients [19] - Fecal occult blood testing has a high false-positive rate in HD (approximately 15% vs. 5% general population) due to uremic platelet dysfunction and heparin use; fecal immunochemical test (FIT) is preferred over guaiac-based testing [41] - Colonoscopy bowel prep can cause electrolyte disturbances, dehydration, and hemodynamic instability - Modeling study: CRC screening adds only 2.6 days of life for non-waitlisted dialysis patients vs. 12 days for transplant recipients [42] - In a large USRDS cohort (469,574 patients), screening was appropriately targeted toward lower-risk patients but absolute rates suggested overscreening in some groups [19]

Prostate Cancer: - PSA levels are frequently elevated in dialysis patients independent of malignancy, reducing specificity - No dialysis-specific PSA screening guideline exists - Individualize based on transplant candidacy and expected survival

Breast Cancer: - Mammographic interpretation may be complicated by vascular and metastatic soft tissue calcifications - Standard screening for transplant candidates with adequate expected survival - No dialysis-specific modification recommended

Cervical Cancer: - Standard screening guidelines apply for transplant candidates - Limited data on cervical cancer risk specific to ESKD

Section Summary

Cancer screening in HD patients must be individualized based on transplant candidacy, expected survival, and patient goals. The ASN Choosing Wisely campaign recommends against routine screening in patients with limited life expectancy. Transplant candidates should receive standard age-appropriate screening. For non-candidates with less than 5-year expected survival, the harms of screening — false positives, procedural complications, anxiety — likely outweigh the minimal mortality benefit. FIT is preferred over guaiac-based FOBT. PSA and mammography have reduced specificity in ESKD due to uremic platelet dysfunction and vascular calcifications, respectively.

7.1 Acquired Cystic Kidney Disease (ACKD) — Epidemiology

ACKD is one of the most underrecognized complications of long-term dialysis. Defined as the development of three or more cysts in each kidney in a patient with CKD and no history of hereditary cystic disease, its prevalence increases dramatically with dialysis duration [21,22]:

A 2025 systematic review and meta-analysis in the World Journal of Surgical Oncology confirmed a standardized incidence ratio (SIR) of 4.7 for kidney and renal pelvis cancer in dialysis patients compared to the general population [24]. This is not a theoretical risk. It is a measurable, dose-dependent complication of dialysis duration.

7.2 Risk of Renal Cell Carcinoma

ACKD carries a markedly elevated risk of renal neoplasia [21-24]:

• RCC risk is 50- to 100-fold higher than the general population
• Overall incidence of ACKD-associated RCC: 3-7% of ESKD native kidneys
• ACKD-RCC is the most common RCC subtype in both ACKD (40%) and ESKD (30%) — recognized as a distinct entity in the 2022 WHO Classification of Renal Tumors
• Tumors are frequently multifocal (approximately 50%) and bilateral (approximately 9%)
• Occurs approximately 20 years earlier than sporadic RCC
• Predominantly affects males (3:1 male-to-female ratio)
• Frequently asymptomatic (approximately 86%); symptoms when present include hematuria, flank pain, or abrupt unexplained hematocrit changes

7.3 Pathogenesis

The 2022 WHO Classification recognizes ACKD-RCC as a distinct renal tumor subtype. The pathogenesis involves a chronic multifactorial milieu [21,43]:

• Uremic toxin exposure and impaired cellular immunity
• Oxidative stress and reactive oxygen species generation
• Oxalate crystal-induced chronic tubular injury
• Growth factor-driven compensatory tubular epithelial proliferation
• Potential proto-oncogene activation in the setting of chronic cellular turnover

The progression follows a stepwise pathway: damaged renal tubule -> simple cyst -> cyst with atypical epithelial lining -> adenoma -> carcinoma. This stepwise model supports the rationale for surveillance — there is a detectable premalignant phase [21].

7.4 Histologic Features

ACKD-RCC has characteristic features distinguishing it from other RCC subtypes [43]:

• Predominantly eosinophilic cells with granular cytoplasm
• Variable cribriform (“sieve-like”), solid, and papillary architecture
• Intratumoral oxalate crystals — characteristic but not required for diagnosis
• Background cystic renal parenchyma
• CAIX negative (vs. positive in clear cell RCC)
• CK7 usually negative (vs. positive in papillary RCC)
• Overall indolent behavior, though 10-15% present with recurrence or distant metastases

7.5 Screening Recommendations

There is no universal guideline for RCC screening in dialysis patients. The KDIGO 2020 Transplant Candidate guideline recommends ultrasonographic screening for renal cell carcinoma in patients at increased risk — including those with >= 3 years on dialysis, family history of renal cancer, ACKD, or analgesic nephropathy [44]. For the general (non-transplant-candidate) dialysis population, an individualized approach is recommended.

Suggested screening protocol:

Imaging modality selection:

Management of detected lesions:

Section Summary

ACKD develops in over 90% of patients on dialysis for more than 10 years and carries a 50- to 100-fold increased RCC risk. The 2022 WHO Classification recognizes ACKD-RCC as a distinct tumor subtype. Ultrasound screening should begin at 3 years of dialysis — the inflection point where ACKD prevalence rises sharply — with annual surveillance thereafter. CT with contrast is the definitive characterization tool (no nephrotoxicity concern in dialysis-dependent patients). This is a critically underrecognized screening opportunity: the premalignant phase is detectable, the tumors are frequently asymptomatic, and early intervention changes outcomes.

8.1 Anemia Monitoring

Anemia is universal in ESKD and requires structured monitoring to guide ESA and iron therapy. The KDIGO 2012 Anemia Guideline provides the framework [45]:

Monitoring schedule:

Key principles: - ESA hyporesponsiveness (failure to achieve target Hb despite adequate ESA dosing) should prompt evaluation for iron deficiency, inflammation, occult blood loss (GI), hyperparathyroidism, B12/folate deficiency, hemoglobinopathy, or malignancy — not reflexive dose escalation - IV iron is preferred over oral iron in HD patients due to poor GI absorption and convenience of administration during dialysis sessions - Upper hemoglobin limit: KDIGO recommends against intentionally exceeding Hb 13 g/dL with ESA therapy (1A), based on the CHOIR and CREATE trials demonstrating increased cardiovascular events and mortality with higher Hb targets [45]

8.2 Nutritional Assessment

Protein-energy wasting (PEW) affects 20-50% of maintenance HD patients and is independently associated with increased morbidity and mortality. A 2024 systematic review and meta-analysis in Clinical Nutrition demonstrated a pooled mortality hazard ratio of 1.49 (95% CI: 1.36-1.64) for malnourished dialysis patients across 29 cohort studies — the kind of effect size that should drive routine screening [46].

Monitoring parameters:

International Society of Renal Nutrition and Metabolism (ISRNM) criteria for PEW diagnosis: Requires at least one criterion in three of four categories: 1. Low serum chemistry (albumin < 3.8 g/dL, prealbumin < 30 mg/dL, cholesterol < 100 mg/dL) 2. Low body mass (BMI < 23, unintentional weight loss > 5% over 3 months) 3. Reduced muscle mass (mid-arm muscle circumference decrease > 10%) 4. Low dietary intake (protein < 0.8 g/kg/day or energy < 25 kcal/kg/day for > 2 months)

8.3 Cardiovascular Screening

Cardiovascular disease accounts for the majority of deaths in ESKD patients. Structured cardiovascular assessment includes:

Echocardiography: - At HD initiation — baseline assessment of LV function, chamber dimensions, valvular calcification, and pericardial disease - Every 1-3 years — surveillance for progressive LV hypertrophy (present in 70-80% of HD patients), diastolic dysfunction, and valvular calcification - After volume optimization — echocardiography performed on the day after dialysis (when closest to “dry weight”) provides the most accurate assessment of LV function - Key findings to monitor: LV mass index, ejection fraction, mitral/aortic valve calcification, pericardial effusion, RV systolic pressure (pulmonary hypertension screen)

ECG: - At initiation and periodically - Primary role: detect electrolyte-driven arrhythmias (hyperkalemia, hypocalcemia), QTc prolongation, and conduction abnormalities - HD patients are at high risk of sudden cardiac death — the leading cause of cardiovascular mortality in ESKD — driven by rapid electrolyte shifts during and immediately post-dialysis

Stress testing: - For transplant candidacy evaluation per institutional protocols - Not routinely recommended for asymptomatic HD patients who are not transplant candidates - The diagnostic accuracy of stress testing is reduced in ESKD due to high prevalence of LVH, baseline ECG abnormalities, and chronotropic incompetence

8.4 Vaccination

HD patients have impaired humoral and cellular immune responses, resulting in lower seroconversion rates and faster antibody waning compared to the general population. Vaccination before dialysis initiation — when immune function is better preserved — produces superior responses [13,29].

Recommended vaccines for HD patients:

8.5 Depression and Cognitive Screening

Depression: Depression affects 20-40% of HD patients — some studies report rates as high as 50% using validated screening instruments. It is independently associated with [26-28]:

• Increased all-cause mortality (HR approximately 1.5-2.0)
• Increased hospitalization rates
• Missed dialysis treatments (a direct predictor of mortality)
• Decreased quality of life and treatment adherence
• Higher likelihood of withdrawal from dialysis

Screening: The PHQ-9 is validated for use in dialysis populations. The PHQ-2 serves as a rapid screen (2 questions); positive results should trigger full PHQ-9 assessment. Screening at HD initiation and at least annually is appropriate — more frequent screening (every 6 months) may be warranted given the high prevalence and fluctuating course [26-28].

Cognitive Impairment: Cognitive impairment is highly prevalent and underrecognized in HD populations, with estimates ranging from 10% to 80% depending on the assessment tool and definition used. A 2025 study in Cureus documented the co-occurrence of cognitive dysfunction and depression in HD patients, highlighting significant unmet diagnostic needs [47].

Key considerations: - Uremic encephalopathy — cognitive deficits from retained uremic toxins; partially reversible with adequate dialysis - Vascular cognitive impairment — from chronic cerebral small vessel disease driven by hypertension, diabetes, and uremic vasculopathy - Dialysis-related cognitive fluctuations — cognitive performance is often worse in the hours following dialysis (osmotic shifts, hemodynamic instability) - Dementia prevalence — substantially higher in ESKD than age-matched controls

Screening with the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE) should be considered at initiation and periodically, particularly in patients with functional decline, nonadherence, or unexplained behavioral changes.

8.6 Dialysis Adequacy Monitoring

While not traditionally considered a “screening test,” dialysis adequacy is the most fundamental monitoring parameter in HD:

• Single-pool Kt/V (spKt/V): Monthly; target >= 1.4 per session for thrice-weekly HD (KDOQI 2015) [51]
• Urea reduction ratio (URR): Alternative adequacy metric; target >= 70%
• Residual kidney function: Assess periodically in patients with residual urine output; contributes to overall solute clearance and may allow reduced dialysis prescription

Section Summary

Health maintenance in HD extends well beyond the disease-specific domains covered in earlier sections. Anemia monitoring (monthly CBC, quarterly iron studies) guides ESA and iron therapy. Protein-energy wasting affects 20-50% of HD patients with a mortality HR of 1.49 — monthly albumin and annual SGA are the minimum. Cardiovascular screening with echocardiography at initiation and every 1-3 years detects the progressive cardiomyopathy and valvular disease that drive the leading cause of death. Vaccination requires an HD-specific approach with high-dose formulations and pre-dialysis timing whenever possible. Depression (20-40%) and cognitive impairment (10-80%) are prevalent, undertreated, and treatment-modifying. Dialysis adequacy with monthly Kt/V rounds out the monitoring framework.