Acute phosphate nephropathy after bowel cleansing: still a menace
Acute phosphate nephropathy after bowel cleansing: still a menace
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Santos, A. Branco, S. Silva, A. Paiva, J. Baldaia, J. Maximino, A. Loureiro, R. Henrique" "autores" => array:8 [ 0 => array:4 [ "Iniciales" => "P." "apellidos" => "Santos" "email" => array:1 [ 0 => "paulo.ads@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "A." "apellidos" => "Branco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "S." "apellidos" => "Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "A." "apellidos" => "Paiva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "Iniciales" => "J." "apellidos" => "Baldaia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 5 => array:3 [ "Iniciales" => "J." "apellidos" => "Maximino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 6 => array:3 [ "Iniciales" => "A." "apellidos" => "Loureiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 7 => array:3 [ "Iniciales" => "R." "apellidos" => "Henrique" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Nephrology Unit, Internal Medicine Department, Pedro Hispano Hospital, Matosinhos, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Department of Pathology, Portuguese Institute of Oncology, Porto, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Acute phosphate nephropathy after bowel cleansing: still a menace" ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dear editor:</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Colonoscopy is critically dependent on adequate pre-procedural bowel cleansing and oral sodium phosphate bowel purgatives (OSP) have been used with good acceptance and efficacy for this purpose<span class="elsevierStyleSup">1</span>. Among others metabolic and clinical disturbances described after the procedure, acute kidney injury may be a serious complication<span class="elsevierStyleSup">2,3</span>. We present two cases of sodium phosphate induced acute renal failure.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 1</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara">A 84 year-old male with a past history of stage 3 obstructive chronic renal failure, prostatic hypertrophy and hypertension, medicated with losartan, presented with complaints of six months weigh loss and changed bowel habits.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A colonoscopy was performed after preparation with oral sodium phosphate solution (Fleet phosphosoda<span class="elsevierStyleSup">®</span>) with standard dose and its result was normal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A week later, the patient reported pedal and orbital oedema and was observed on the emergency department. The physical examination was unremarkable except for hypertension (180/80 mmHg) and lower limbs oedema. Laboratory results showed haemoglobin 11.1 g/dl, serum urea 346 mg/dl, serum creatinine 9.2 mg/dl, serum sodium 130 mEq/L, serum potassium 6.5 mEq/L, serum phosphorus 6.6 mg/dl, normal serum calcium, serum bicarbonate 15 mEq/L and mild proteinuria. Serum and urine immunoelectrophoresis and immunologic study were normal. Renal ultrasound showed increased cortical echogenicity. Haemodialysis was initiated. Kidney biopsy showed minimal mesangial expansion. The tubules were mildly dilated and focal interstitial fibrosis was present. Von Kossa stain positive deposits were observed within the cytoplasm of tubular epithelial cells, tubular lumen and interstitium (figure 1 and figure 2). Immunofluorescence was negative for immunoglobulin or complement.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We made the diagnosis of acute phosphate nephropathy secondary to administration of a sodium phosphate purgative.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Renal dysfunction didn’t improve after 7 months and the patient continues on regular haemodialysis.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 2</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">A 88 year-old male with a past history of prostatic hypertrophy and marginal zone-B cell lymphoma IV-B stage (treated with vincristine, cyclophosphamide and prednisolone for two cycles followed by second line therapy with rituximab and chlorambucil with disease progression) and stage 4 obstructive chronic renal failure. A virtual colonoscopy was performed after bowel preparation with Fleet phosphosoda<span class="elsevierStyleSup">®</span>. Colonic diverticulosis was diagnosed.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Five days latter the patient reported lethargy and anuria and was admitted on the emergency department. He presented with drowsiness and was hypotensive, apyretic and oliguric. He presented inspiratory crackles on chest exam, distended and painful abdomen without guarding and lower limb oedema. Abnormal test results were hemoglobin 9.7 g/dL, leucocytes 17.1 x 10<span class="elsevierStyleSup">9</span>/L (87% neutrophils), platelets 70 x 10<span class="elsevierStyleSup">9</span>/L, serum creatinine 3.45 mg/dL, serum urea 106 mg/dL, serum calcium 4.5 mg/dl, serum phosphorus 18.3 mg/dL, lactate dehydrogenase 3,028 U/L, c-Reactive protein 28.2 mg/dL, pH 7.3, bicarbonate 13.3 mEq/L and lactate 7.5 mmol/L; Urine dipstick was positive for blood, leucocytes and proteins. Renal ultrasound showed kidneys with enhanced echogenicity. Chest radiograph showed interstitial oedema and abdominal radiograph was normal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Suspected severe urinary sepsis and acute kidney injury secondary to sepsis and phosphate nephropathy were assumed. Intravenous fluid was started, samples were obtained for culture and broad spectrum antibiotics were started. There was no clinical improvement and conservative measures were adopted.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Acute phosphate nephropathy (AphN) is a form of kidney injury that occurs after the use of bowel purgatives that contain oral sodium phosphate (OSP)<span class="elsevierStyleSup">2</span>. OSP bowel solution (Fleet phosphosoda<span class="elsevierStyleSup">®</span>) is a hyperosmotic purgative that has been used with good acceptance and efficacy in bowel cleansing before colonoscopy<span class="elsevierStyleSup">1</span>. Both patients made the standard regimen (two 45 ml doses taken 10-12 h apart). Each dose contains monobasic and dibasic sodium phosphate providing the equivalent of 5,8 g of elemental phosphorus and 5 g of sodium<span class="elsevierStyleSup">3</span>. Intestinal absorption occurs and transient hyperphosphatemia and hypocalcemia are found in all patients<span class="elsevierStyleSup">2</span>. However, severe hyperphosphatemia, symptomatic hypocalcemia, hypernatremia, symptomatic hyponatremia, hypokalemia, anion-gap acidosis and acute kidney injury have been described after the procedure<span class="elsevierStyleSup">3-6</span>. Two different clinical patterns of OSP-induced acute kidney injury have been described: early symptomatic and late insidious<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The earlier form consists in an acute illness that manifests as changes in mental status, tetany, or cardiovascular collapse, usually in hours of bowel preparation, and patients present with severe hyperphophatemia and hypocalcemia. The second patient presented fit in this category. These patients require urgent fluid resuscitation, rapid correction of electrolyte disturbances, and sometimes dialysis. Despite aggressive fluid replacement and resuscitation our patient died. Some patients with this presentation survive and show renal function recovery<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The second form is due to AphN with a more insidious onset (days to months) and is generally irreversible<span class="elsevierStyleSup">1</span>. At the time of diagnosis, serum phosphorus and calcium levels are normal, unless measured within 3 days of bowel preparation. This was in fact the case of the first patient. As we found, the main pathologic finding in kidney biopsy is nephrocalcinosis demonstrated with the Von Kossa stain<span class="elsevierStyleSup">1</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Following reports of AphN Fleet phosphosoda<span class="elsevierStyleSup">®</span> was voluntary withdrawn from US market in 2008<span class="elsevierStyleSup">10</span>. However OSP solution is still in use in some countries, as Portugal.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The pathophysiology of APhN involves transient hyperphospatemia, volume depletion exacerbated by concurrent ACE-I, ARB and diuretics, and elevated distal tubular phosphate and calcium concentrations<span class="elsevierStyleSup">1,8,10</span>. Risk factors include advanced age, chronic kidney failure, dehydratation, female gender, diuretics, a history of colitis, and, probably, diabetes mellitus and non-steroidal anti-inflammatory drugs<span class="elsevierStyleSup">1,10</span>. Data indicate a high risk for chronic renal failure<span class="elsevierStyleSup">1,9,10</span>. Our first patient needed long term haemodialysis. In Markowitz series none patient returned to their baseline creatinine levels and 19% progressed to ESRD at mean of 13.8 months after colonoscopy<span class="elsevierStyleSup">9</span>.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">In conclusion, these cases highlight the importance of AphN because such OSP are still used in clinical practice. Clinical presentation may assume two forms and, in any of these, consequences are serious and sometimes fatal. Strategies to prevent the development of APhN should be adopted and include avoidance in high-risk patients, adequate hydratation, dose minimization,  increasing the interval between doses and possibly not administering ACE-I, ARB, diuretics and NSAID on the day before and the day after colonoscopy procedure<span class="elsevierStyleSup">6,10</span>. It is also advisable to perform serum biochemistry tests after the procedure, in order to detect any renal or electrolyte abnormalities<span class="elsevierStyleSup">7</span>.</p><p class="elsevierStylePara"><a href="grande/10544_108_6841_en_10544_f1.jpg" class="elsevierStyleCrossRefs"><img src="10544_108_6841_en_10544_f1.jpg" alt="Kidney biopsy. Von Kossa coloration (40x). "></img></a></p><p class="elsevierStylePara">Figure 1. Kidney biopsy. Von Kossa coloration (40x). </p><p class="elsevierStylePara"><a href="grande/10544_108_6843_en_10544_f2.jpg" class="elsevierStyleCrossRefs"><img src="10544_108_6843_en_10544_f2.jpg" alt="Kidney biopsy. Von Kossa coloration (100x)."></img></a></p><p class="elsevierStylePara">Figure 2. Kidney biopsy. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 5 | 0 | 5 |
| 2024 Octubre | 51 | 0 | 51 |
| 2024 Septiembre | 51 | 0 | 51 |
| 2024 Agosto | 79 | 0 | 79 |
| 2024 Julio | 51 | 0 | 51 |
| 2024 Junio | 64 | 0 | 64 |
| 2024 Mayo | 81 | 0 | 81 |
| 2024 Abril | 63 | 0 | 63 |
| 2024 Marzo | 53 | 2 | 55 |
| 2024 Febrero | 66 | 13 | 79 |
| 2024 Enero | 45 | 14 | 59 |
| 2023 Diciembre | 45 | 8 | 53 |
| 2023 Noviembre | 86 | 9 | 95 |
| 2023 Octubre | 88 | 7 | 95 |
| 2023 Septiembre | 71 | 11 | 82 |
| 2023 Agosto | 56 | 5 | 61 |
| 2023 Julio | 68 | 8 | 76 |
| 2023 Junio | 81 | 17 | 98 |
| 2023 Mayo | 100 | 11 | 111 |
| 2023 Abril | 44 | 9 | 53 |
| 2023 Marzo | 63 | 14 | 77 |
| 2023 Febrero | 57 | 10 | 67 |
| 2023 Enero | 72 | 10 | 82 |
| 2022 Diciembre | 93 | 19 | 112 |
| 2022 Noviembre | 68 | 16 | 84 |
| 2022 Octubre | 77 | 23 | 100 |
| 2022 Septiembre | 93 | 15 | 108 |
| 2022 Agosto | 87 | 20 | 107 |
| 2022 Julio | 71 | 20 | 91 |
| 2022 Junio | 67 | 13 | 80 |
| 2022 Mayo | 92 | 17 | 109 |
| 2022 Abril | 73 | 21 | 94 |
| 2022 Marzo | 61 | 18 | 79 |
| 2022 Febrero | 66 | 26 | 92 |
| 2022 Enero | 102 | 27 | 129 |
| 2021 Diciembre | 83 | 19 | 102 |
| 2021 Noviembre | 79 | 19 | 98 |
| 2021 Octubre | 79 | 24 | 103 |
| 2021 Septiembre | 62 | 18 | 80 |
| 2021 Agosto | 72 | 30 | 102 |
| 2021 Julio | 69 | 20 | 89 |
| 2021 Junio | 78 | 13 | 91 |
| 2021 Mayo | 101 | 11 | 112 |
| 2021 Abril | 231 | 26 | 257 |
| 2021 Marzo | 111 | 19 | 130 |
| 2021 Febrero | 108 | 14 | 122 |
| 2021 Enero | 102 | 12 | 114 |
| 2020 Diciembre | 64 | 7 | 71 |
| 2020 Noviembre | 72 | 6 | 78 |
| 2020 Octubre | 57 | 6 | 63 |
| 2020 Septiembre | 76 | 6 | 82 |
| 2020 Agosto | 78 | 4 | 82 |
| 2020 Julio | 77 | 7 | 84 |
| 2020 Junio | 72 | 15 | 87 |
| 2020 Mayo | 80 | 9 | 89 |
| 2020 Abril | 73 | 20 | 93 |
| 2020 Marzo | 80 | 16 | 96 |
| 2020 Febrero | 86 | 11 | 97 |
| 2020 Enero | 111 | 15 | 126 |
| 2019 Diciembre | 85 | 18 | 103 |
| 2019 Noviembre | 71 | 13 | 84 |
| 2019 Octubre | 39 | 4 | 43 |
| 2019 Septiembre | 63 | 16 | 79 |
| 2019 Agosto | 53 | 7 | 60 |
| 2019 Julio | 50 | 19 | 69 |
| 2019 Junio | 51 | 9 | 60 |
| 2019 Mayo | 53 | 12 | 65 |
| 2019 Abril | 89 | 18 | 107 |
| 2019 Marzo | 42 | 14 | 56 |
| 2019 Febrero | 45 | 16 | 61 |
| 2019 Enero | 42 | 12 | 54 |
| 2018 Diciembre | 130 | 27 | 157 |
| 2018 Noviembre | 121 | 18 | 139 |
| 2018 Octubre | 97 | 25 | 122 |
| 2018 Septiembre | 54 | 11 | 65 |
| 2018 Agosto | 66 | 16 | 82 |
| 2018 Julio | 80 | 15 | 95 |
| 2018 Junio | 55 | 17 | 72 |
| 2018 Mayo | 66 | 16 | 82 |
| 2018 Abril | 57 | 12 | 69 |
| 2018 Marzo | 58 | 14 | 72 |
| 2018 Febrero | 50 | 8 | 58 |
| 2018 Enero | 48 | 10 | 58 |
| 2017 Diciembre | 51 | 6 | 57 |
| 2017 Noviembre | 51 | 10 | 61 |
| 2017 Octubre | 43 | 12 | 55 |
| 2017 Septiembre | 43 | 10 | 53 |
| 2017 Agosto | 50 | 10 | 60 |
| 2017 Julio | 52 | 9 | 61 |
| 2017 Junio | 54 | 9 | 63 |
| 2017 Mayo | 65 | 9 | 74 |
| 2017 Abril | 75 | 6 | 81 |
| 2017 Marzo | 50 | 2 | 52 |
| 2017 Febrero | 41 | 5 | 46 |
| 2017 Enero | 22 | 3 | 25 |
| 2016 Diciembre | 57 | 2 | 59 |
| 2016 Noviembre | 87 | 11 | 98 |
| 2016 Octubre | 116 | 61 | 177 |
| 2016 Septiembre | 141 | 8 | 149 |
| 2016 Agosto | 226 | 0 | 226 |
| 2016 Julio | 177 | 0 | 177 |
| 2016 Junio | 132 | 0 | 132 |
| 2016 Mayo | 154 | 0 | 154 |
| 2016 Abril | 106 | 0 | 106 |
| 2016 Marzo | 63 | 0 | 63 |
| 2016 Febrero | 104 | 0 | 104 |
| 2016 Enero | 115 | 0 | 115 |
| 2015 Diciembre | 143 | 0 | 143 |
| 2015 Noviembre | 105 | 0 | 105 |
| 2015 Octubre | 99 | 0 | 99 |
| 2015 Septiembre | 72 | 0 | 72 |
| 2015 Agosto | 81 | 0 | 81 |
| 2015 Julio | 100 | 0 | 100 |
| 2015 Junio | 44 | 0 | 44 |
| 2015 Mayo | 110 | 0 | 110 |
| 2015 Abril | 22 | 0 | 22 |
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