A 62-year-old man with CKD 5 (eGFR 11 mL/min) due to HTN comes to the clinic for routine follow-up with no complaints of nausea, vomiting, fatigue, or poor appetite. An arterio-venous fistula (AVF) was placed 1 year ago when his eGFR was 12 mL/min and the fistula is ready for use. His BP is 134/80 mmHg. He walks 2 miles everyday without shortness of breath, or chest pain, or fatigue. Pertinent labs include: Na⁺ 139 mEq/L, K⁺ 4.4 mEq/L, HCO₃ ⁻ 22 mEq/L, BUN 68 mg/dL, Ca²⁺ 8.8 mg/dL, phosphate 4.2 mg/dL, and albumin 4.1 g/dL. He expresses hemodialysis (HD) as his choice of renal replacement therapy (RRT) . According to the KDIGO guideline, which one of the following is the MOST appropriate management in this patient?

Of all the choice, choice D is appropriate. According to the KIDIGO guideline, dialysis should be considered when signs and symptoms of kidney failure such as serositis, acid–base or electrolytes abnormalities, pruritis are present. In addition, dialysis should be initiated when volume status and BP cannot be controlled. Thus, D is correct. The patient wants HD when appropriate. Convincing him at this time for preemptive kidney transplantation is unwise. The patient wishes to have HD rather than PD. Starting PD and suggesting conservative management are not appropriate at this time.

Which one of the following statements in CKD 5 patients regarding early (eGFR 10–14 mL/min) versus late (eGFR 5–7 mL/min) initiation of HD is CORRECT?

Except for one study, there are no large studies that evaluated the outcomes of early versus late initiation of HD. Cooper et al. randomized 828 adults (mean age 60.4 years) in 32 centers in Australia and New Zealand to begin early or late HD treatment. During the median follow-up of 3.59 years, 37 % in the early-start group and 36.6 % in the late-start group died. Also, there was no difference between the groups in cardiovascular events, infections, or complications of dialysis . The median time to initiation of dialysis was 1.8 months in the early-start groups compared to 7.4 months in the late-start group. Therefore, the correct answer is C.

It should be remembered that this study cannot be extrapolated to all ethnic group because the majority of the study patients were under the care of a nephrologist (approximately 32.5 months for the early group and 29.4 months for the late group), and such a follow-up may not be available to most other patients. Also, 70–73 % of the patients were whites. Therefore, initiation of RRT should be individualized.

Which one of the following decisions is important for conservative management of patients with ESRD is CORRECT?

For some patients with ESRD, offering conservative (palliative) care may be a satisfactory alternative to RRT. In a survey of nephrologists from 11 European countries, a decision was made to offer conservative care for 15 % (10 % by nephrologists, and 5 % by patients) of patients in 2009. Patients’ preference (93 %), severe clinical conditions (93 %), vascular dementia (84 %), and low physiological functional status (75 %) were considered important in the decision-making of not to start RRT.

In another study from Australia, about 14 % of patients with CKD 5 preferred conservative care when presented as a treatment option. The median age of these patients was 80 years. Of interest is that those patients with private health insurance did not prefer conservative care. Therefore, the option of conservative care should be presented to certain patients who do not benefit from dialysis.

A 56-year-old woman is started on hemodialysis (HD) using a fistula that was created 1 year ago. She is diabetic with HTN. Which one of the following dialysis prescriptions is APPROPRIATE to improve dialysis outcomes?

In addition, the guideline recommends the use of synthetic high-flux membranes to delay or reduce long-term complications of HD therapy, such as dialysis-related amyloidosis, to improve hyperphosphatemia, to reduce cardiovascular risk, and to improve anemia.

You started a 50-year-old man with eGFR 7 mL/min on HD 3 times per week because of poor appetite. He has a functiona l AVF created 9 months ago. The patient wants more frequent in-center HD sessions in preparation for home HD in the future, and he wants to know the benefits and risks associated with frequent HD. Which one of the following choices regarding the risks and benefits of frequent HD is CORRECT?

Several small studies have shown better outcomes in patients who received frequent HD treatments. Compared to these small studies, a larger study with 245 patients on frequent in-center HD was published in 2010. In this study, called Frequent Hemodialysis Network (FHN) trial, 125 patients were allocated to conventional HD (3 times per week) and 120 patients to 6 times per week schedule. The study duration was 12 months. The following table shows the study design, and characteristics, and achieved time, fluid removal (ultrafiltration, UF), and Kt/v of the study (Table 9.1 ).

The following improved outcomes were observed:

Adverse events

No changes were observed in:

Thus, E is correct. However, the FHN Nocturnal Trial, which included only 87 patients (45 conventional HD, and 42 nocturnal HD) did not find any difference in any of the above observations.

Six months later, the above patient showed interest in home HD. Which one of the following regarding home HD compared to in-center HD is CORRECT?

There are no specific guidelines to address the selection of RRT for patients with ESRD; many nephrologists offer several options to patients with ESRD, including preemptive transplantation, conservative care, and other dialysis modalities. If the patient’s preference is dialysis, either peritoneal dialysis or home HD is recommended. Although there are more patients on in-center HD, the preference for home HD is increasing. The prevalence rate of home HD varies from 5 to 15 %. The most important prerequisite for home HD is the patient’s willingness or partner who is able to perform dialysis safely. The suitability of home environment for HD will then be assessed.

Weinhandl and colleagues reviewed the evidence for survival rate between daily home HD and matched thrice-weekly in-center HD patients and concluded that risk of death in the former treatment group was 13 % and 18 % lower in intention-to-treat and as-treated analyses, respectively. They attributed this lower risk of death in daily home HD patients to reduced cardiovascular and other unknown causes. Also, another study by Stack and colleagues showed that home HD patients are 26 % less likely to die compared to in-center HD patients. Thus, these reports suggest survival benefit in patients who are on home HD (C is correct).

A 60-year-old thin small woman on a 4-h session HD 3 times per week asks you to reduce her time to 3½-h, as her eKt/V is 1.4. Her post-dialysis BP is 150/86 mmHg, and interdialytic weight gain is 3 kg. Which one of the following choices regarding short in-center HD is CORRECT?

In this thin and small person, a longer session time and maintenance of Kt/V of 1.4 is recommended by the HEMO study.

Fluid gain during interdialytic HD treatments is a risk factor for all-cause and cardiovascular (CV) mortality. Your patient with congestive heart failure (CHF) who weighs 80 kg gained 5 kg between 2 successive treatments. Which one of the following is the desired and recommended ultrafiltration (UF) rate in this patient?

Interdialytic fluid gain is rather common in many HD patients. Patients who have excess fluid gain are at increased risk for HTN, LVH, CHF, and CV-associated mortality. At the start of HD, each patient is prescribed an estimated dry weight (EDW), which is defined as “the lowest tolerated post-dialysis weight achieved with minimal signs or symptoms of hypo- or hypervolemia.” Although this definition is incomplete, most of the nephrologists try to achieve EDW in their patients. This requires frequent adjustment of EDW because of weight gain due to fluid intake, Na ⁺ intake or improvement in nutritional status.

Despite adequate education, some patients have excess interdialytic weight gain of >2.5 L. In such patients, Data from the Hemodialysis (HEMO) study showed that UF rate >13 mL/h/kg was associated with increased all-cause or CV mortality. UF rates between 10 and 13 mL/h/kg were not associated with all-cause or CV mortality, but they were significantly higher in patients with CHF. Cubic spine analysis showed that a steep rise in the risk for all-cause and CV mortalities at UF rates >10 mL/h/kg. Thus, UF rate 10 mL/h/kg seems appropriate (C is correct), and other UF rates or removal of the entire gained volume are inappropriate in this patient. Additional treatments or longer treatment sessions may be appropriate to achieve EDW in this patient.

The above patient received several additional sessions of HD with an UF rate of 10 mL/h/kg. His eKt/v is 1.3, and serum albumin is 4.1 g/dL. His interdialytic weight gain is 1.6 kg with fluid and Na⁺ restriction. His BP at time of dialysis initiation is 144/82 mmHg. During one of his sessions, he started developing hypotension without any UF. His hypotension improves with administration of 500 mL of normal saline. During the next HD session, the patient develops intradialytic hypotension. Which one of the following approaches seems reasonable to improve his hypotension?

The appropriate choice to improve his intradialytic hypotension is reevaluation of his EDW (D is correct). Lowering EDW may prevent the development of hypotension. Lowering his antihypertensive medication may increase his predialysis BP, and Na ⁺ modeling will raise his serum Na ⁺ as well as thirst. Without addressing his dry weight, saline infusion should not be continued, and midodrine is inappropriate in this patient as his predialysis BP is adequate.

A 52-year-old man is being dialyzed 3 times per week on high-flux dialyzer for removal of fluid at 10 mL/h/kg for an interdialytic weight gain of 4 kg. Despite adequate education from the dietician, physician, and additional dialysis session, his interdialytic weight gain did not improve. He says he is depressed because of family troubles, and he does not want to take any antidepressants. Besides Na ⁺ restriction in diet, which one of the following therapeutic modalities will improve his interdialytic weight gain?

Cukor et al. evaluated the efficacy of individual chairside cognitive behavioral therapy in 33 HD depressive patients and 26 wait-list control group on depression, quality of life, and fluid adherence for 3 months. The effect was assessed at 3 and 6 months. Depression was measured in three different ways. Overall, the study showed that individual cognitive behavioral therapy is effective in improving depression scores, fluid adherence, and quality of life (C is correct). However, this positive effect did not last after 6 months, suggesting the requirements for persistent cognitive behavioral therapy.

Other choices such as fluid restriction, switching him to PD or home dialysis are not appropriate for this patient. It is known that UF >15 mL/h/kg is associated with increased cardiovascular morbidity, and should not be applied for any fluid overloaded patient.

Hemodiafiltration (HDF) combines both diffusion and convection. Although HDF is not available in the United States, it is used in Europe. Which one of the following clinical benefits of HDF is FALSE?

HDF is a modality that combines both diffusion and convection. This technique requires large ultrapure volumes of replacement fluid. This fluid can be infused pre-, post-, or mixed dilution modes. Because of convection, many uremic toxins that have a molecular weight up to 40,000 Da can be removed. As a result, many biochemical abnormalities associated with ESRD or uremia can be improved. Removal of middle molecules such as β ₂ -microglobulin is 30–40 % higher with HDF compared to high-flux dialysis. Similarly removal of phosphate mass with HDF is 15–20 % higher than other HD modalities. It has been shown that cytokine removal is much higher with HDF, and preservation of residual renal function is prolonged with HDF. However, most studies did not find any significant benefit of HDF in improving nutritional, as measured by either albumin or prealbumin concentrations. Thus, E is false.

HDF has been shown to improve β ₂ -microglobulin -associated amyloidosis and carpal tunnel syndrome. Also, some studies have shown reduced incidence of intradialytic hypotensive episodes. However, most studies showed no effect of HDF on the usage of erythropoietic stimulating agents and anemia.

Regarding survival benefit of hemodiafiltration (HDF), which one of the following choices is CORRECT?

The third study by Maduell et al. from Spain showed that HDF with postdilution infusion of convection volume between 23 and 25 L/session and >25 L/session caused a 40 % and 45 % mortality risk reduction, respectively. Also, other outcomes such as cardiovascular mortality, hospitalization, and intradialytic hypotensions were much lower in those patients who received HDF. This study confirmed the post hoc analyses of the first and second studies, suggesting that HDF with convections volumes >23 L/session can improve patient survival and other adverse events. Thus, option E is correct.

In hemodiafiltration, ultrapure dialysate and nonpyrogenic substitution fluid are generally used. Some of the complications observed in HD patients have been attributed to contaminants such as bacteria and endotoxins in ultrapure dialysate. Which one of the following choices regarding ultrapure dialysate is FALSE?

Except choice D, all other choices are correct. The Association for the Advancement of Medical Instrumentation reduced the target limits of viable bacteria and endotoxin to <0.1 CFU/mL and 0.03 EU/mL, respectively, for ultrapure dialysate and to <200 CFU/mL and 2 EU/mL, respectively, for standard dialysate. Thus, choices A and B are correct. Cuprophane and polyacrylonitrile dialysis membranes are more permeable to endotoxins and promote inflammatory cytokine production than polysulfone and polyamide dialysis membranes (C is correct). Because of this high permeability of certain membranes, inflammatory cytokine levels are high in the serum of dialysis patients. Also, the levels of these cytokines are dependent on the level of endotoxin that enter the blood via the permeable membranes (E is correct). However, there are no randomized trials to confirm that ultrapure dialysate is superior to standard dialysate in reducing the cytokine levels and associated complications. Thus, D is false.

However, the use of ultrapure dialysate has been reported to improve anemia, dialysis-related amyloidosis, and nutritional status. Also, reduction in mortality was reported by some studies.

A 51-year-old woman with multiple myeloma (biopsy-proven cast nephropathy) is admitted with a serum creatinine of 10.6 mg/dL and [Ca²⁺] of 11.8 mg/dL. She is started on thalidomide and bortezomib, and hemodialysis (HD). She responded initially to chemotherapy , but became resistant to the second cycle of chemotherapy. She is continued on HD. She asks you about high cutoff HD (HCO-HD). Which one of the following statements is CORRECT regarding HCO-HD is FALSE?

The most common cause of acute kidney injury (AKI) in patients with multiple myeloma is cast nephropathy. The casts are composed of monoclonal FLC and Tamm-Horsfall protein that are formed in the distal and collecting ducts, and cause tubular obstruction and atrophy with the release of inflammatory cytokines. The net result is interstitial damage and fibrosis .

Light chains are of two types: k-chains and λ-chains with molecular weights of 22,500 and 45,000 Da, respectively. These FLCs are freely filtered at the glomerulus and reabsorbed by the proximal tubules. The proximal tubule cannot handle the excess production of these FLC in multiple myeloma, resulting in cast formation and tubular obstruction. Therefore, extracorporeal therapies have been used in addition to chemotherapy to remove the excess FLC. Rapid reduction of FLC has been shown to improve renal function .

Plasmapheresis removes FLC because these are confined to the extracellular space. A 2-h treatment is able to remove only 25 % of these FLCs, and rebound of these FLCs is substantial following discontinuation of plasmapheresis. Probably this is one of the reasons for the lack of effect of plasmapheresis on the recovery of renal function in one of the larger studies involving 104 patients with AKI. Similarly, high-flux HD cannot remove these FLCs unless hemodiafiltration is applied.

In order to achieve a better removal of FLCs, the HCO-HD was introduced. In this technique, the hemofilters with large pores that can remove proteins with 45,000–65,000 Da and large surface area 1.1–2.1 m ² have been developed. Using one of these filters, a few clinical trials, involving 5, 19, and 67 patients, showed that >50 % of patients improved their renal function without dialysis. However, this improvement was seen in those patients who responded to chemotherapy . Nonresponders did not improve their renal function. Therefore, HCO-HD cannot be applied to all patients (D is false). One of the major problems with these clinical trials is lack of appropriate controls. Therefore, the renal recovery in >50 % of patients cannot be attributed to HCO-HD alone. So far two randomized trials are underway to address the efficacy of HCO-HD, and until the results are available, the answer to the patient question is that the HCO-HD may not be helpful to her.

In your patient with CKD 4 (eGFR 22 mL/min), you plan to place a native arterio-venous (A-V) fistula. Which one of the following is the MOST preferred fistula for your patient?

Currently there are several options for creation of vascular accesses at different anatomical locations of the body. In general, the preferred initial site is the wrist in a nondominant arm. Therefore, the radiocephalic access is the preferred A-V fistula for any patient (A is correct). Once distal sites are exhausted, creation of a fistula in the upper arm should be considered, and brachiocephalic or brachiobasilic fistula s are placed. The A-V graft has less survival compared to the fistula, and is not the preferred access in most of the patients. The concept of FISTULA FIRST is introduced because of superior outcomes with a fistula compared to a graft.

The above patient has radiocephalic fistula , and he comes to your office 4 weeks after fistula creation. Which one of the following measurements suggests that the fistula is functioning properly and will be ready in 3 months for cannulation?

Generally 28–53 % of A-V accesses never mature adequately to be usable for dialysis . When mature, the median time for maturity is 98 days. The KDOQI guidelines defined the “rule of 6s” as the criteria for maturation of the fistula, which include (1) vein diameter of 6 mm, (2) access flow rate of 600 mL/min, and (3) access depth of 6 mm below the skin. According to the study of Robbin et al. the vein diameter >4 mm and access flow rate >500 mL/min are highly predictive of fistula maturation and adequate for cannulation. Based on these criteria, choice D is correct, suggesting that the fistula is maturing properly. Other choices are incorrect.

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